The ESTHER database


   

The superfamily of alpha/beta hydrolase fold was defined by structural homology. (Follow this link for a list of selected bibliographic references on alpha/beta hydrolases). The three dimensional structures of the lipases from the fungus Geotrichum candidum (GCL) and human pancreas as well as the structure of acetylcholinesterase revealed a very similar topology of the central beta-sheet and the same location of two (Ser,His) of the three residues comprising the catalytic triad.
Although these proteins show little sequence homology, the conservation of the topology suggests that these proteins diverged from a common ancestor (Ollis et al. 1992). The figure on the left (click on the icon) is a schematic diagram of the common features of the structure. It consists of a central 5 to 11 stranded beta-sheet in which most strands are parallel (example of order of strands are 12435678 or 21345). This sheet is flanked on both sides by alpha-helices. The core of the structure can be represented as follows:



       

Now many more proteins were shown to belong also to the superfamily. These include carboxypeptidase II from wheat, dienelactone hydrolase from Pseudomonas, haloalkane dehalogenase from Xanthobacter, cutinase from Fusarium solani,Vibrio harveyi thioesterase, Xanthomonas campestris proline iminopeptidase etc.... The superfamily also now includes many peptidases, and epoxide hydrolases. Now Interpro .AB_hydrolase and Superfamily .SSF53474 cover most alpha/beta hydrolases

There are 228 subfamilies as seen in the list of Tables or the table overallTable (old synthese) Now at least 663 different proteins have been crystallized and shown to belong to the superfamily (view liste) . There are 131 families in which at least one protein structure is known. There are 2808 files in the PDB (Protein DataBase ) containing coordinates of native enzymes, or complexes with inhibitors or models. Links to those files are included in the structure chapter of ESTHER or (view liste) .
The diagrams of these have been grouped in a figure: Figure of all
Note A number of structure some of which have been mentionned here as being part of the family, indeed have another fold: the Serine esterase from Streptomyces scabies (1esc), the platelet-activaing-factor acetylhydrolase from Bos taurus (1wab) and rhamnogalacturonan acetylesterase from Aspergillus aculeatus (1deo),the haemagluttinin esterase fusion glycoprotein from Influenza virus C (1flc)

Our mistake was brought to our attention by Dr. Derewenda and Dr. Mølgaard (see reference Molgaard, Kauppinen & Larsen (2000) Structure, 8:373-383) A name for this family was proposed SGNH-hydrolase. These structures are included in the SCOP database under the Flavodoxin-like fold, the Esterase/acetylhydrolase super family This may include now also the GDSL lipolytic enzymes (for example E. Coli thioesterase/protease I) and the PFAM family PF00657 GDSL-like Lipase/Acylhydrolase
Note The family Zn-dependent_exopeptidase had been mentionned as having some similarities with alpha/beta hydrolase fold family in the paper Ollis et al. 1992. Now it seems they should not be included in the alpha/beta hydrolase fold family. This Zn-dependent_exopeptidase family might be mentionned as "in-laws" together with the SGNH-hydrolase family and the chemotaxis protein CheB. We acknowledge and would like to follow the classifications of experts in the field Heikinheimo P, Goldman A, Jeffries C, Ollis DL (1999)Of barn owls and bankers: a lush variety of alpha/beta hydrolases Structure Fold Des 7:R141-6
Note A fold : (Flavodoxin-like) groups now SGNH hydrolase superfamily Class I glutamine amidotransferase-like superfamily (containing DJ-1/PfpI family), and many others... These are close to alpha beta hydrolases and some time referred as such in papers but are not included in ESTHER
Note Some families group carbohydrates esterase classified as families 1,3,5,7,10 in the CAZy (Carbohydrate-Active enZYmes server )
Note Some families contain lipolytic enzymes from bacteria that have been classified originally by Arpigny and Jaeger in 1999 and updated by Jaeger and Eggert in 2002, Hausmann and Jaeger (2010), Kovacic, Krauss and Jaeger (2019). Correspondance between the classification is found in the following table: Arpigny_Jaeger table. Note that Family II and Family VIII in this classification are not alpha/beta hydrolases but SGNH hydrolases and beta lactamases respectively and are not represented in ESTHER

No other database than ESTHER holds all alpha/beta hydrolase fold proteins together:Interpro, Prosite, Pfam, have multiple entries for subsets of this structural superfamily. A table overallTable shows the correspondance between these database entries and the subfamilies in ESTHER. Now Interpro .AB_hydrolase and Superfamily .SSF53474 fulfill this task also.
The ESTHER old table is now a little to big to be usefull. Each file contains one of the 65099 non redundant proteins/genes. The tables grouped in the overallTable (old: family table, syntheses table) or the structure table may be more usefull.
The Gene_locus nomenclature for these non-redundant entries is a name with 5 characters for the organisms (3 for genera, 2 for the species, except when a common 5 character name exists. ex: ratno is for Rattus norvegicus and human for man. This allows us to keep close to the Swiss-Prot nomenclature). The last characters define the protein, ex: human-ACHE represents human acetylcholinesterase.

       
During evolution stuctural similarity is preserved much longer than sequence similarity.
Although the server ESTHER presents information on all alpha/beta hydrolase fold proteins it focuses on a smaller group of proteins of the superfamily for which sequence homology can be detected. This group of sequences includes cholinesterases, carboxylesterases, lipases, and some non enzymatic domains of other proteins (Krejci et al. 1991; Gentry and Doctor 1991; Cousin et al., 1996).A schematic drawing of the relationship of these protein subfamilies follows. (click on the tree icon)


       The sequence homologies of these subtypes suggests that they derive from a common ancestor. Although some sequences show little homology, some blocks are conserved.These BLOCKS were used to select sequences for the ESTHER database.On the BLOCK page you will find the definitions and the prototypes of the sequences which have the PROSITE "signature" (PSOO122) of carboxylesterase/cholinesterase called here the C-family, or (PS00120) of lipase called here the L-family. Hemila et al.(1994) described another group of related enzymes HSL (for hormone sensitive lipases).This group also contains some bacterial lipases. We have, since then, included these genes/sequences in the database as the H-family.New prosite entries have been created (september 1996) for this group of sequences ps01173 and ps01174.
This confirms the identity of this H subfamily.

Different families of proteases also belong to the alpha/beta fold structural family. (See the peptidase liste, and the Merops database) These are until now all included in the SC clan of families of the Serine-type peptidases.For the moment, families S9 (except S9D?) S10 S15 S28 S33 are alpha/beta hydrolases
The S9 family (Prolyl oligopeptidase, Dipeptidyl-peptidase IV, Acylaminoacyl-peptidase) has a PDOCfile PDOC00587, the S10 family (Carboxypeptidase C) has a PDOCfile PDOC00122, the S15 family (Lactococcus X-Pro dipeptidyl-peptidase), the S28 family (Lysosomal Pro-X carboxypeptidase)


Block C FamilyComment
ACHE

Acetylcholinesterase (ACHE; EC 3.1.1.7) controls synaptic and neurohumoral cholinergic activity by hydrolyzing the neurotransmitter acetylcholine. ACHE function relies on precise regulation of its expression and localization. In particular, alternative splicing of the 3-prime region of ACHE results in ACHE isoforms with distinct C-terminal peptides that determine posttranslational maturation and oligomeric assembly. Acetylcholinesterase is also found on the red blood cell membranes, where it constitutes the Yt blood group antigen.

BCHE

Acylcholine acylhydrolase, Butyrylcholine esterase, Choline esterase II, Pseudocholinesterase. Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters. BChE deficiency is a metabolic disorder characterized by prolonged apnoea after the use of certain anesthetic drugs, including the muscle relaxants succinylcholine or mivacurium and other ester local anesthetics.Various autosomal recessive mutations of the gene exist in human population

Carboxylesterase

Higher eukaryotes have many distinct esterases. The different types include those that act on carboxylic esters (EC 3.1.1). Carboxyl-esterases have been classified into three categories (A, B and C) on the basis of differential patterns of inhibition by organophosphates. Here are B type. WARNING There is no Plant carboxylesterases in this family except an EST from sorgho (sorbi-cxest) which could be a contaminant. Plant carboxylesterases do not possess SEDCLYLN and are included in a specific family: Plant_carboxylesterase. This family corresponds to the Carbohydrate Esterase family CE10 in CAZy - Carbohydrate-Active enZYmes database (CE_10). For bacterial enzymes this family correspond to family VII of the classification of Arpigny and Jaeger (1999)

Carb_B_Annelida

This family was extracted from the previous Carboxylesterase COesterase family.

Carb_B_Arthropoda

Carboxylesterases of insects have been subdivided in clades A to M (Claudianos 2006 Ranson 2002). With the Dietary class (clades ABC), the Pheromone/hormone processing class (clades D to G), the Neuro/developmental class (H to M). The present family Carb_B_Arthropoda corresponds to clades ABC. Members of these clades are important in detoxifixtion of insecticides .Gene amplifications or point mutations leading to resistance. Clades D to M have their own family (AChE, JHE, Glutactin Neuroligin, Neurotactin). This family was extracted from the previous Carboxylesterase COesterase family. This family corresponds to the Carbohydrate Esterase family CE10 in CAZy - Carbohydrate-Active enZYmes database (CE_10).

Carb_B_Bacteria

This family was extracted from the previous Carboxylesterase COesterase family. Not all bacteria possess esterase with the SEDCLYLN signature. This family corresponds to the Carbohydrate Esterase family CE10 in CAZy - Carbohydrate-Active enZYmes database (CE_10). As bacterial enzymes this family correspond to family VII of the classification of Arpigny et al 1999

Carb_B_Brachiopoda

This family was extracted from the previous Carboxylesterase COesterase family. This family corresponds to the Carbohydrate Esterase family CE10 in CAZy - Carbohydrate-Active enZYmes database (CE_10).

Carb_B_Chordata

This family was extracted from the previous Carboxylesterase COesterase family. This family corresponds to the Carbohydrate Esterase family CE10 in CAZy - Carbohydrate-Active enZYmes database (CE_10). Mammalian liver carboxylesterases (CESs; EC 3.1.1.1) hydrolyze various xenobiotics and endogenous substrates with ester, thioester, or amide bonds and are thought to function mainly in drug metabolism and detoxication of harmful chemicals. CES1 is also responsible for hydrolysis of stored cholesterol esters in macrophage foam cells and release of free cholesterol for high density lipoprotein-mediated cholesterol efflux

Carb_B_Mollusca

This family was extracted from the previous Carboxylesterase COesterase family. This family corresponds to the Carbohydrate Esterase family CE10 in CAZy - Carbohydrate-Active enZYmes database (CE_10).

Carb_B_Nematoda

This family was extracted from the previous Carboxylesterase COesterase family. This family corresponds to the Carbohydrate Esterase family CE10 in CAZy - Carbohydrate-Active enZYmes database (CE_10). A subset of this family is isolated as Esterase CM06B1-like family in Interpro IPR043187.

Carb_B_Root

This family was extracted from the previous Carboxylesterase COesterase family. it contains putative esterase from eucaryotes (not insects nematodes or chordates)

Cholesterol_esterase

The human lactating mammary gland and pancreas produce a lipolytic enzyme, carboxyl-ester lipase, earlier called bile salt-stimulated lipase. Carboxyl-ester lipase is a major component of pancreatic juice and is responsible for the hydrolysis of cholesterol esters as well as a variety of other dietary esters. The enzyme is activated when mixed with bile salts, and plays an important role in the digestion of milk fat in newborn infants. This enzyme combines properties of esterases (activity on esters soluble in water) and lipases (activity on insoluble long chain acylglycerols) Numerous repeats at the c-term excluded in ESTHER (only n-term Pfam A COesterase 1 544)

Cholinesterase

Acetylcholinesterase (ACHE; EC 3.1.1.7) controls synaptic and neurohumoral cholinergic activity by hydrolyzing the neurotransmitter acetylcholine. ACHE function relies on precise regulation of its expression and localization. In particular, alternative splicing of the 3-prime region of ACHE results in ACHE isoforms with distinct C-terminal peptides that determine posttranslational maturation and oligomeric assembly

Cholinesterase-like

Analysis of the complete genome sequences of numerous representatives of the various metazoan phyla show that moderate amplification of cholinesterase genes is not uncommon in molluscs, echinoderms, hemichordates, prochordates or lepidosauria. Amplification of acetylcholinesterase genes is also a feature of parasitic nematodes or ticks. This family is now called Cholinesterase like. It also contains sequences very close to AChE but which are either incomplete or are missing W84 or one of the residue of the catalytic triad or are pseudogenes with deletions or errors of conceptual splicing Before this family was called Dictyostelium_crys as it contained only Dict proteins. These proteins have an active site serine and have probably an esterase activity but are in membrane-enclosed crystals and probably have non catalytic functions.

Fungal_carboxylesterase_lipase

This family was extracted from the previous Carboxylesterase COesterase family. Carboxylesterase, type B (COesterase) is very successful in fungi. Grouped with Lipase_3 in Family Fungal lipases in scop database. This family corresponds to the Carbohydrate Esterase family CE10 in CAZy - Carbohydrate-Active enZYmes database (CE_10) LED_Database abH03 abH02. The presence of a water/lipid interface dramatically enhances the hydrolytic activity of lipases. The activation is associated with a conformational change. The Ser-His-Asp/Glu catalytic triad is occluded by a polypeptide flap (lid) and is not exposed to the solvent until the lid is open. A protein of this family lacking the catalytic serine is a dirigent protein which controls the stereoselectivity of multicopper oxidase(VdtB)-catalyzed phenol coupling in viriditoxin biosynthesis (Hu et al. 2019)

Gliotactin

Gliotactin, a transmembrane protein on peripheral glia, is required to form the blood-nerve barrier in Drosophila. It is a marker of tricellular junctions, is necessary for septate junction development in Drosophila. Gliotactin and Discs large form a protein complex at the tricellular junction of polarized epithelial cells in Drosophila. The intracellular domain of gliotactin, is natively unfolded. Control of Gliotactin localization and levels by tyrosine phosphorylation and endocytosis is necessary for survival of polarized epithelia

Glutactin

Insect specific protein. Glutactin has a signal peptide and an amino domain of greater than 500 residues that strongly resembles acetylcholine esterases and other serine esterases, but lacks the catalytically critical serine residue. It is located at embryonic basement membranes, particularly to the sequentially invaginated envelope of the central nervous system, muscle apodemes and dorsal median cell processes. Ectopic expression of Glutactin inhibits synapse formation by motor neurons that normally innervate M12 muscle. Only the N-terminal part of Glutactin is a member of the alpha/beta hydrolase family. The C-terminal part is not included in ESTHER

Juvenile_hormone_esterase

Juvenile hormone JH is an insect hormone containing an alpha,beta-unsaturated ester consisting of a small alcohol and long hydrophobic acid. JH degradation is required for proper insect development. One pathway of this degradation is through juvenile hormone esterase JHE which cleaves the JH ester bond to produce methanol and JH acid. Another way of degradation of JH is epoxyde hydrolysis. Most insect species contain only juvenile hormone (JH) III. To date JH 0, JH I, and JH II have been identified only in the Lepidoptera (butterflies and moths). The form JHB3 (JH III bisepoxide) appears to be the most important JH in the Diptera, or flies. Certain species of crustaceans have been shown to produce and secrete methyl farnesoate, which is juvenile hormone III lacking the epoxide group. Methyl farnesoate is believed to play a role similar to that of JH in crustaceans. In drosophila DmJHE is the hormone esterase with precise regulation and highly specific activity for its substrate, juvenile hormone. DmJHEdup is an odorant degrading esterase (ODE) responsible for processing various kairomones in antennae

Neuroligin

Neuroligins constitute a family of proteins thought to mediate cell-to-cell interactions between neurons. Neuroligins function as ligands for the neurexin family and MADD-4. This interaction is necessary for GABA receptors clustering. Mammals have four Nlgn proteins, with the Nlgn3 and Nlgn4 gene in humans localised to the X-chromosome. In humans, the Nlgn4 gene is complemented on the Y-chromosome by a similar Nlgn4Y gene.(from OMIM) In 2 brothers with autism, one with typical autism and the other with Asperger syndrome, Jamain et al. (2003) identified a frameshift mutation (1186T) in the human-NLGN4X gene, resulting in a stop codon at position 396 and premature truncation of the protein before the transmembrane domain. The mutation was present in the mother and absent in an unaffected brother and 350 controls. See other contradictory results Gauthier et al. Vincent et al., but other mutations found Laumonnier et al. Yan et al. Incomplete penetrance suspected for some mutations. In 2 brothers with autism, one with typical autism and the other with Asperger syndrome, Jamain et al. (2003) identified a mutation R451C in the human-NLGN3 gene. arg451 in NLGN3, arg386 in BCHE, and arg395 in ACHE are conserved in mammalian species. In cellular transfection studies, De Jaco et al. (2006) inserted mutations homologous to the NLGN3 R451C mutation in BCHE and ACHE cDNAs and found that these mutations resulted in endoplasmic reticulum retention of the 2 proteins, similar to that observed with the NLGN3 R451C mutant protein. Tabuchi et al. (2007) introduced the R451C substitution in neuroligin-3 into mice. R451C mutant mice showed impaired social interactions but enhanced spatial learning abilities. Unexpectedly these behavioral changes were accompanied by an increase in inhibitory synaptic transmission with no apparent effect on excitatory synapses. Deletion of neuroligin-3, in contrast, did not cause such changes, indicating that the R451C substitution represents a gain-of-function mutation. Tabuchi et al. (2007) concluded that increased inhibitory synaptic transmission may contribute to human autism spectrum disorders and that the R451C knockin mice may be a useful model for studying autism-related behaviors. Recently Venkatesh et al. showed that neuronal activity promotes glioma growth through Neuroligin-3 secretion. Recently Neuroligin 2 mutations were associated with anxiety, autism, intellectual disability, hyperphagia, and obesity.Many mutations on X-linked cell NLGN4X result in ASD or intellectual disability. NLGN4Y cannot compensate for the functional deficits due to NLGN4X mutations

Neurotactin

Only the C-terminal part of Neurotactin is a member of the alpha/beta hydrolase family. The N-terminal part of Neurotactin has low complexity is desordered and is intracellular. Neurotactin is found only in arthropods Neurotactin is only detected during cell proliferation and differentiation, and it is found mainly in neural tissue and also in mesoderm and imaginal discs. Neurotactin has a large cytoplasmic domain rich in charged residues and an extracellular domain similar to cholinesterase that lacks the active site serine required for esterase activity. Amalgam is a ligand for the transmembrane receptor neurotactin and is required for neurotactin-mediated cell adhesion and axon fasciculation in Drosophila. Mutants of neurotactin revealed specific requirements for neurotactin during axon outgrowth, fasciculation, and guidance.

Non-catalytic_C

This family contains genes/protein of the COesterase group which lack some of the active site residues (neuroligins, neurotactin, gliotactin, glutactin)

OtherNon-catalytic_C

Among COesterase PF00135 a number of proteins seem to lack active site residues but have not yet been characterized. They are not related to the known families of non-catalytic COesterase (neuroligins, neurotactin, gliotactin, glutactin) They could be pseudo genes or sequencing errors

Thyroglobulin

Only the C-terminal part of thyroglobulin is a member of the alpha/beta hydrolase family, here starting with the first G in cholinesterase 2206 (aa numbering in human thyroglobulin). The N-terminal part of thyroglobulin is made of three domains, labeled I to III, that encompass 10 repeats of a ca. 65 amino acid residues known as the Tg type-1 repeat PF00086 PS00484 IPR011641 IPR000716 not included in ESTHER. Thyroglobulin is the glycoprotein precursor to the thyroid hormones T3 (triiodothyronine) and T4 (tetraiodothyronine). It has a molecular mass of 660 kD, with 2 identical subunits, yet its complete hydrolysis yields only 2 to 4 molecules of T3 and T4. The protein contains a 19-amino acid signal peptide followed by 2,748 residues. Van Ommen (1987) suggested that defects in the TG gene can cause either dominant or recessive disorders depending on the nature of the defect. When the gene is absent or at least when no thyroglobulin is synthesized, the disorder is likely to be recessive, whereas the presence of an abnormal subunit leads to a dominantly inherited disorder. The explanation for this is that in a dimeric protein such as thyroglobulin, 75% of the dimers in heterozygotes will contain 1 or more abnormal subunits. This should profoundly disturb thyroglobulin metabolism, since this protein fulfills a dual storage/catalytic role as a dimer, is present in bulk quantities (100 mg Tg/g thyroid mass), and needs to be exocytosed, iodinated, endocytosed, and degraded. EnsemblClone AF230666, EnsemblContig AC079020.2.132816.152274, AF235100_2 gene chromosome 8 clone PAC 98A24 map 8q24.3. there is a small gene with only a little bit of thyroglobuline just 3' of the real gene AC069434.7.189089.192039 ENST00000254617 ENSG00000132287. Three out of five iodination sites are in the cholinesterase homologous domain 2573 (In T4), 2587 (In T4),2766 (In T3)


Block H FamilyComment
Arylacetamide_deacetylase

AADAC Arylacetamide deacetylase displays cellular triglyceride lipase activity in liver, increases the levels of intracellular fatty acids derived from the hydrolysis of newly formed triglyceride stores and plays a role in very low-density lipoprotein assembly. Displays serine esterase activity in liver. Deacetylates a variety of arylacetamide substrates, including xenobiotic compounds and procarcinogens, converting them to the primary arylamide compounds and increasing their toxicity. NCEH1 KIAA1363 AADACL1 NCEH1 neutral cholesterol ester hydrolase 1.is highly expressed in invasive cancer cells and is the major protein in mouse brain diethylphosphorylated . Sequence similarities between hormone-sensitive lipase and prokaryotic enzymes was dicovered by Langin and Holm and Hemila et al.

BD-FAE

Extracted from Hormone sensitive lipases. BD-FAE: The function of many members may differ from the one of the representavive used to describe the family in the PFAM database. (from PFAM): This family represents a novel bifunctional feruloyl and acetyl xylan esterase (BD-FAE, previously known as bifunctional carbohydrate esterase (CE)), which is active on complex natural xylans and was identified as the basis of a monophyletic clade gathering all homologs identified in PULs (polysaccharide utilisation loci) predicted to act on xylan. It adopts an alpha-beta-hydrolase fold with the catalytic triad Ser-Asp-His. This new family of proteins is a new candidate for biomass processing due to its capacity to remove ferulic acid and acetic acid from natural corn and birchwood xylan substrates. In PFAM database it includes family Tannase_Bact and family Est9X which are separate families in ESTHER

Est9X

Bacterial esterases. Fang et al. described a novel esterase from a marine metagenomic library exhibiting high salt tolerance. The enzyme is essentially active on pNP-C2 C4 and C6. The family is extracted from 6_AlphaBeta_hydrolase. This family differs from all the families of the Arpigny Jaeger classification.

GTSAGmotif

Sequences of lipases from metagenomic library were grouped in a new subset of Alphabeta hydrolase fold-3 (Arpigny_Jaeger Family_IV). Most sequences have a G(TDC)SA(G)G motif encompassing the active site serine.

Hormone-sensitive_lipase_like

Sequence similarities between hormone-sensitive lipase and prokaryotic enzymes was dicovered by Langin and Holm and Hemila et al.. The family Corresponds to the Pfam entry Abhydrolase_3. For bacterial enzymes this family correspond to family IV of the classification of Arpigny et al 1999

Kynurenine-formamidase

Kynurenine formamidase (EC:3.5.1.9) catalyses the hydrolysis of N-formyl-L-kynurenine to L-kynurenine, the second step in the kynurenine pathway of tryptophan degradation. It is required for elimination of toxic metabolites

Plant_carboxylesterase

No plant Carboxylesterase show the SEDCLYLN motif (prosite PS00941). These carboxylesterase are related to the Hormone sensitive lipase. Gibbereline Insensitive Dwarf1 GID1 has a primary structure similar to that of the hormone-sensitive lipase. Gibberellins (GAs) are tetracyclic, diterpenoid plant hormones, essential for many developmental processes in higher plants HSLs. The nuclear GA receptor evolved from an esterase. 2-hydroxyisoflavone dehydratase from leguminosae also belong to this family, in these particular enzymes the catalytic serine is replaced by threonine. In tulips tuliposide-converting enzyme (TCE) purified from tulip bulbs catalyzed the conversion of tuliposides to tulipalins.The lactone-forming carboxylesterases, specifically catalyzing intramolecular transesterification, but not hydrolysis

Steryl_acetyl_hydrolase

Sterol homeostasis in eukaryotic cells relies on the reciprocal interconversion of free sterols and steryl esters. In Saccharomyces cerevisiae (Baker's yeast) sterol acetylation requires the acetyltransferase Atf2, whereas deacetylation requires Say1, a membrane-anchored deacetylase with a putative active site in the ER lumen. Lack of Say1 results in the secretion of acetylated sterols into the culture medium, indicating that the substrate specificity of Say1 determines whether acetylated sterols are secreted from the cells or whether they are deacetylated and retained. In S. cerevisiae cells lacking Say1 or Atf2 are sensitive against the plant-derived allylbenzene eugenol and both Say1 and Atf2 affect pregnenolone toxicity, indicating that lipid acetylation acts as a detoxification pathway (old DUF2424)

Tannase_Bact

This family of bacterial tannases close to hormone sensitive lipases, differs from the (Tannase) tannases and feruloyl esterase of fungi and bacteria grouped in the tannase family. The first structure described by Ren et al. Matoba et al. in this family presents a large cap domain inserted after the beta 7 strand of classical alpha/beta hydrolases. Tannases hydrolyze the galloyl ester bond in tannins to release gallic acid


Block L FamilyComment
Avian-virus_vlip

This family has been recognized as alpha/beta hydrolase by Kamil et al. Previously associated with Lipoprotein_lipase family but is also close to phospholipase. vLIP may not serve as a traditional lipase enzyme, but the serine nucleophile position is essential in vivo for the viral functions of vLIP. Could be example of repurposing alpha/beta hydrolase fold toward a nonenzymatic role, possibly in lipid bonding

Bacterial_lipase

This family correspond to family I.1, I.2, I.3, I.5, I.6, (families I.4 and 1.7 are more related to Lipase_2) of the classification of Arpigny and Jaeger (1999).(also included in IPR000734) Also close to Lipase_2 (2lip). Pseudomonas cepacia lipase is in the same family of scop as 1I6W bacillus subtilis lipase).

Bacterial_lip_FamI.1

This family corresponds to family I.1 of the classification of Arpigny and Jaeger (1999)

Bacterial_lip_FamI.2

This family corresponds to family I.2 of the classification of Arpigny and Jaeger (1999)

Bacterial_lip_FamI.3

This family corresponds to family I.3 of the classification of Arpigny and Jaeger (1999) The N-catalytic domain (residues 1370) contains the active site residues, Ser207, Asp255, and His313 4, 5. The C-domain contains several repeats of the RTX motif and a putative secretion signal near the C-terminus. The Cdomain contains two beta-roll motifs, laterally stacked together forming the so called beta-roll sandwich. The first beta-roll motif consists of residues 373417, containing five RTX repeats and binds three Ca2+ ions. The second beta-roll motif consists of residues 493-568, containing eight RTX repeats and binds five Ca2+ ions. HemolysinCabind (PF00353). This family contains Polyurethanases (PURase)

Bacterial_lip_FamI.5

This family correspond to family I.5 of the classification of Arpigny and Jaeger (1999) and abH15 of the LED database. It includes lipases from gram positive bacteria, organic-solvent tolerant, showing thermoalkalophilic properties and high molecular weight resulting from extra domain where a zinc ion is coordinatively bound to the enzyme. The family also contains poly (butylene adipate-co-terephthalate)-hydrolyzing lipase from Pelosinus fermentans

Bacterial_lip_FamI.6

This family correspond to family I.6 of the classification of Arpigny and Jaeger (1999). These lipases differ from other bacterial lipases. They present high phospholipase A1 activity. The substrate-binding cavity contains two large hydrophobic acyl chain-binding pockets and a shallow and more polar third pocket that is capable of binding either a (short) fatty acid or a phospholipid head-group.

Canar_LipB

The lead of this family is Candida antarctica (Trichosporon oryzae) (yeast) Lipase B. It was previously embedded in Lipase_3. The family corresponds to the _abH37 - Candida antarctica lipase like_ family of the LED database. Lipase B from Candida antarctica (CALB) has broad substrate specificity and high enantioselectivity. It can function in aqueous and organic environments and is used for a wide range of applications such as transesterification, and polymerization reactions, asymmetric synthesis

Chlorophyllase

This family consists of several plant specific Chlorophyllase proteins (EC: 3.1.1.14). Chlorophyllase (Chlase) is the first enzyme involved in chlorophylle (Chl) degradation and catalyses the hydrolysis of ester bond to yield chlorophyllide and phytol The family includes both plant bacteria and Amphioxus members. However Chlorophyllase is not localized to plastids, and double knockout mutant plants still are able to degrade chlorophyll during leaf senescence. So pheophytinase is a new pathway. Chlorophyllase could be more important in fruit rippening

Hepatic_Lipase

Pancreatic, hepatic and gastric/lingual lipase are closely related to each other and to lipoprotein lipase (EC: 3.1.1.34), which hydrolyses triglycerides of chylomicrons and very low density lipoproteins (VLDL). Familial human hepatic lipase deficiency is a rare recessive disorder Two variants (S267F and T383M) are rare mutations found to date only in HL deficient subjects and their relatives. Of the six HL variants described to date, only S267F and T383M are associated with hyperlipidemia. human-LIPC. The disease is characterised by premature atherosclerosis and abnormal circulating lipoproteins

Insect_lipase

This family groups insect lipases close to mammalian pancreatic, hepatic and gastric/lingual lipase which are closely related to each other and to lipoprotein lipase (EC: 3.1.1.34), which hydrolyses triglycerides of chylomicrons and very low density lipoproteins (VLDL). These are neutral lipases distinct from Acidic lipases and higher dipteran yolk proteins

Insect_Phospholipase

Phospholipase A(1) (PLA(1)) is an enzyme that hydrolyzes phospholipids and produces 2-acyl-lysophospholipids and fatty acids and is conserved in a wide range of organisms. Included in this family are Vespid venom allergen phospholipase A1. Vespid phospholipase A1 (vPLA1) is one of the primary venom components with local inflammatory effects. In addition to causing allergic reactions, vPLA1 can hydrolyze the sn-1 fatty acids in phospholipids and convert them into their corresponding lyso compounds. vPLA1 may disrupt the phospholipid packing of biological membranes, causing severe hemolysis and leading to cardiac dysfunction and death in animals

Lipase_3

Triglyceride lipases are lipases that hydrolyse ester linkages of triglycerides. These lipases are widely distributed in animals, plants and prokaryotes. This family was also called class 3 lipases as they are only distantly related to other lipase families. In some fungi DDHD domain Pfam PF02862 180 residues long containing four conserved residues that may form a metal binding site is associated with the Lipase_3. Feruloyl esterases are enzymes produced by micro-organisms to deconstruct plant cell walls by hydrolyzing phenolic groups involved in the cross-linking of arabinoxylan to other polymeric structures. The non-modular type-A feruloyl esterase from Aspergillus niger AnFaeA is similar to fungal lipases and different from other feruloyl esterases. Bacterial enzymes (LipG Lee et al. 2006) belong to family XI of the classification of Arpigny and Jaeger 1999. The (phospho)lipase of F. solani has the highest microbial activity on galactolipids Jallouli et al.

Lipoprotein_Lipase

Lipoprotein lipase (LPL) is a key enzyme of lipid metabolism that hydrolyses triglycerides, providing free fatty acids for cells and affecting the maturation of circulating lipoproteins. The enzyme is thought to play a role in the development of obesity and atherosclerosis. Defects in LPL are a cause of familial chylomicronemia syndrome (or type I hyperlipoproteinemia) and also of a form of deficiency characterised by hypertriglyceridemia. Familial chylomicronemia is a recessive disorder usually manifesting in childhood. On a normal diet, patients often present with abdominal pain, hepatosplenomegaly, lipemia retinalis, eruptive xanthomata, and massive hypertriglyceridemia, sometimes complicated with acute pancreatitis. Endothelial lipase (encoded by the LIPG gene) regulates the circulating level of high density lipoprotein cholesterol (HDL-C). It can also form a molecular bridge between endothelial cells and lipoproteins or circulating macrophages through interaction with heparan sulfate proteoglycans. This nonenzymatic action can increase cellular lipoprotein uptake and monocyte adhesion and contribute to atherosclerosis. LPL is a secreted glycoprotein that contains five disulfide bonds and requires an endoplasmic reticulum (ER) protein, lipase maturation factor 1 (LMF1), to successfully fold and traffic out of the ER to the Golgi. LPL is sorted into vesicles in an inactive state: helical LPL oligomer. LPL secretion is mediated by Syndecan-1 (SDC1), a heparan sulfate proteoglycan (HSPG). Stored LPL can be secreted into the interstitial space, where it interacts with HSPGs that bind to the multiple heparin binding sites on each LPL molecule . LPL is next bound by glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) and transported into the capillary, where it acts on chylomicrons and very-low-density lipoproteins (VLDLs) to hydrolyze packaged triglycerides and release FFAs. The angiopoietin-like (ANGPTL) family of proteins inhibit LPL in different tissues. Leth-Espensen et al. publish that the intrinsic instability of the hydrolase domain of lipoprotein lipase facilitates its inactivation by ANGPTL4-catalyzed unfolding.

Pancreatic_lipase

Pancreatic, hepatic and gastric/lingual lipase are closely related to each other and to lipoprotein lipase (EC: 3.1.1.34), which hydrolyses triglycerides of chylomicrons and very low density lipoproteins (VLDL). Pancreatic lipase (triacylglycerol acylhydrolase, EC: 3.1.1.3) plays a key role in dietary fat absorption by hydrolysing dietary long chain triacyl-glycerol to free fatty acids and monoacylglycerols in the intestinal lumen. The activity of lipase is stimulated by colipase in the presence of bile acids. Congenital pancreatic lipase deficiency is a rare, monoenzymatic form of exocrine pancreatic failure. Patients have oily/greasy stools from infancy or early childhood and the absence of discernable pancreatic disease. The pancreatic lipase-related protein show no significant catalytic activity on any of the substrates tested di and tri-glycerides phospholipids. Introducing the double mutation Val 178 Ala and Ala 180 Pro into the human pancreatic RP1 HPLRP1 gene yielded an enzyme is kinetically active on triglycerides. The guinea pig pancreatic lipase-related protein 2 (GPLRP2) differs from classical pancreatic lipases in that it displays both lipase and phospholipase A1 activities; classical pancreatic lipases have no phospholipase activity. human-PNLIPRP2 adopt in solution an open lid conformation which creates a large cavity capable of accommodating the galactose polar head of galactolipids (galactolipase)

PC-sterol_acyltransferase

Lysosomal phospholipase A2 (LPLA2) and lecithin:cholesterol acyltransferase (LCAT) belong to this family of key lipid-metabolizing enzymes responsible for lung surfactant catabolism and for reverse cholesterol transport, respectively. Whereas LPLA2 is predicted to underlie the development of drug-induced phospholipidosis, somatic mutations in LCAT cause fish eye disease and familial LCAT deficiency. LACT also known as phosphatidylcholine-sterol acyltransferase (EC), is involved in extracellular metabolism of plasma lipoproteins, including cholesterol. It esterifies the free cholesterol transported in plasma lipoproteins, and is activated by apolipoprotein A-I. Defects in LACT cause Norum and Fish eye diseases. This family correspond to group XV phospholipase A2. For bacterial enzymes this family correspond to family XIV of the upgraded classification of Arpigny and Jaeger (1999)

Phospholipase

Phospholipase A(1) (PLA(1)) is an enzyme that hydrolyzes phospholipids and produces 2-acyl-lysophospholipids and fatty acids and is conserved in a wide range of organisms. Hypotrichosis, or woolly hair with or without hypotrichosis hypotrichosis (deficiency of hair growth), can be caused by homozygous or compound heterozygous mutation in the LIPH (human-LIPH) gene on chromosome 3q27 (not hepatic lipase: human-LIPC). Other mammalian enzymes that exhibit PLA(1) activity in vitro are hepatic lipase HL endothelial lipase EL and pancreatic lipase-related protein 2 PLRP2 and belong to alpha/beta hydrolase superfamily.

Plant_lipase_EDS1-like

Enhanced Disease Susceptibility 1 (EDS1), an essential component of R gene-mediated disease resistance. The Arabidopsis EDS1 (arath-eds1) and PAD4 (arath-F22O6.190) genes encode lipase-like proteins that function in resistance (R) gene-mediated and basal plant disease resistance. EDS1 can dimerize and interact with PAD4. EDS1 (arath-eds1) and PAD4 (arath-F22O6.190) genes encode lipase-like proteins that function in resistance (R) gene-mediated and basal plant disease resistance. EDS1 can dimerize and interact with PAD4 or with SAG101 (arath-At5g14930). This family is extracted from the Lipase3 gene family. The C-terminal domain known as the EP domain and its interface consists of hydrophobic interactions, salt bridges, and an extensive hydrogen bonding network. Plants utilise intracellular nucleotide-binding, leucine-rich repeat (NLR) immune receptors to detect pathogen effectors and activate local and systemic defence. NRG1 and ADR1 'helper' NLRs (RNLs) cooperate with enhanced disease susceptibility 1 (EDS1), senescence-associated gene 101 (SAG101) and phytoalexin-deficient 4 (PAD4) lipase-like proteins to mediate signalling from TIR domain NLR receptors (TNLs). Two distinct modules (NRG1/EDS1/SAG101 and ADR1/EDS1/PAD4) mediate TNL receptor defence signalling. (In the seed alignment and the HMM alignement the EP domain (not alpha/beta hydrolase domain) is excluded)

Plant_phospholipase

Family close to Lipase_3. The DEFECTIVE IN ANTHER DEHISCIENCE gene encodes a novel phospholipase A1 catalyzing the initial step of jasmonic acid biosynthesis, which synchronizes pollen maturation, anther dehiscence, and flower opening in Arabidopsis. AtDSEL, an Arabidopsis cytosolic DAD1-like acylhydrolase, is involved in negative regulation of storage oil mobilization during seedling establishment. This family is close to Plant_lipase_EDS1-like and belongs to Lipase_3 family

Polyesterase-lipase-cutinase

This family differs substantially from the cutinase acetyl-xylan esterase family. Several cutinases from the genus Thermobifida act on biodegradable plastics such as synthetic polyesters. Not all cutinases can degrade polyester plastics. Aerial plant organs are protected by a cuticle composed of an insoluble polymeric structural compound, cutin, which is a polyester composed of hydroxy and hydroxyepoxy fatty acids. Cutinases are lipases with a specificity for p-nitrophenyl acyl esters with short chain acyl group. This family was extracted from the Bacterial_lipase family which is close to PAF-Acetylhydrolase family. Streptomyces exfoliatus lipase (1JFR) Pseudomonas mendocina lipase (2FX5) are included in this family. This family correspond to family III of the classification of Arpigny et al 1999. Polyethylene terephthalate degrading hydrolase/PET-hydrolase/PET Hydrolase. Two enzymes in Ideonella sakaiensis (for example) act on PET (Poly ethylene terephthalate): idesa-peth from Polyesterase-lipase-cutinase family and idesa-mheth which acts on extremity of PET (Exo-PETase Function) and on MHET the product of hydrolysis of PET. MHETase belongs to the Tannase family

Triacylglycerol-lipase-OBL1-like

Family extracted from Lipase_3. (from InterPro) This family includes triacylglycerol lipase OBL1 from Arabidopsis thaliana and Nicotiana tabacum, which are homologues of the acid lipase from castor bean (RcOBL1). OBL1 is an acid GXSXGlipase localized to lipid droplets that can hydrolyse a range of triacylglycerols without a clear preference for acyl-chains. It can also cleave 1,2-diacylglycerol, 1,3-diacylglycerol and 1-monoacylglycerol, but not phosphatidylcholine, phosphatidylethanolamine, or sterol esters. It is required for pollen tube growth. Triacylglycerol hydrolysis by OBL1 may provide acyl groups for the synthesis of membrane lipids in growing pollen tubes

Yolk-Protein_dipter

These proteins sometimes referred as vitellogenins are specific to higher dipters and are not evolutionnary related to the vitellogenins accumulated in oocytes of most oviparous animals


Block X FamilyComment
5_AlphaBeta_hydrolase

This family corresponds partially to PF12695 (Abhydrolase_5)

6_AlphaBeta_hydrolase

This family corresponds to the residual members of PF12697 Abhydrolase_6 not included in other subfamilies. Mostly badly characterized proteins. Many members of AlphaBeta_hydrolase family belong to this family and should soon be updated

A85-Est-Putative

This family contains enzymes with putative esterase activities corresponding to the Carbohydrate Esterase family CE1 in CAZy - Carbohydrate-Active enZYmes database (CE_1) Members belong to the Antigen85c family but differ from the other characterized sub-families

A85-EsteraseD-FGH

This family contains EC 3.1.2.12, human Esterase D and bacterial S-formylglutathione hydrolase. A universal pathway for formaldehyde detoxification. Corresponds to a subset of the Carbohydrate Esterase family CE1 in CAZy - Carbohydrate-Active enZYmes database (CE_1). Arabidopsis thaliana (Mouse-ear cress) serine esterase s-formylglutathione hydrolase SFGH is insensitive to organophosphate. Family TE22 in ThYme database

A85-Feruloyl-Esterase

Feruloyl esterases play a key role in the degradation of the intricate structure of the plant cell wall by hydrolysing the ferulate ester groups involved in the cross-linking between hemicelluloses and between hemicellulose and lignin. It belongs to a supramolecular assembly termed a cellulosome. This multienzyme complex possesses in addition to its well-described cellulolytic activity an apparatus specific for xylan degradation. Feruloyl esterases, Cinnamic acid esterases hydrolyze the ferulate groups involved in the crosslinking of arabinoxylans to lignin and thus play a key role in the degradation of the plant cell wall. clotm-xyny corresponds to the feruloyl esterase module from a 5 domain xylanase Xyn10B. This family contains enzymes corresponding to a subset of the Carbohydrate Esterase family CE1 in CAZy - Carbohydrate-Active enZYmes database (CE_1) with Ser His Asp catalytic triad. Here most of the A85-Feruloyl-Esterase are bacterial enzymes but there are few fungi proteins that belong to this family and are farther related to the other fungi feruloyl esterase belonging to other families (Tannase (Aspergillus Niger FaeB) ; 6_AlphaBeta_hydrolase, Lipase_3 (Aspergillus Niger FaeA); Esterase_phb (Penicillium funiculosum FaeB Piromyces equi ESTA)

A85-IroE-IroD-Fes-Yiel

This family contains enterobactin esterase IroD, enterochelin Esterase FES enterobactin and salmochelin esterase IroE; The proliferation of many pathogenic bacteria is limited by the scarcity of soluble iron in their environment Many of these bacteria scavenge iron by synthesizing and exporting small molecule siderophores that chelate iron Iron-bound siderophores are subsequently imported for metabolic processing. Three related serine hydrolases have been characterized biochemically in this pathway Fes IroD and IroE; This family corresponds to a subset ofthe Carbohydrate Esterase family CE1 in CAZy - Carbohydrate-Active enZYmes database (CE_1). Active site Ser His Asp or Glu or nothing

A85-Mycolyl-transferase

This family contains Antigen85 responsible for high affinity of mycobacteria for fibronectin. Proteins of the antigen 85 possess a mycolyltransferase activity required for the biogenesis of trehalose dimycolate (cord factor), a dominant structure necessary for maintaining cell wall integrity. Mycobacterium tuberculosis MPT51 (FbpC1) is a non-catalytic alpha/beta hydrolases member of this family. This family corresponds to a subset of the the Carbohydrate Esterase family CE1 in CAZy - Carbohydrate-Active enZYmes database (CE_1)

ABHD6-Lip

Monoacylglycerol lipase ABHD6 hydrolyses the endocannabinoid 2-arachidonoylglycerol (2-AG). 2-AG regulates neurotransmission and neuroinflammation by activating CB1 cannabinoid receptors on neurons and CB2 cannabinoid receptors on microglia. (A MGLL human-MGLL or MAGLL is the other enzyme hydrolyzing 26AG (belongs to Monoglyceridelipase_lysophospholip family). . Alpha/beta-Hydrolase domain 6 deletion induces adipose browning and prevents obesity and type 2 diabetes and is published by Zhao et al.. A study by Wei et al. shows that ABHD6 negatively regulates the surface delivery and synaptic function of AMPA receptors independantly of hydrolase activity. ABHD6 hydrolyzes Bis(monoacylglycerol)phosphate (BMP): a phospholipid crucial for lipid degradation and sorting in acidic organelles and accumulating in Lysosomal storage disorders Pribasnig et al. ABHD6 of animals is homologous to some bacterial enzymes. For bacterial enzymes, this family correspond to family V.1 of the classification of Arpigny and Jaeger 1999 Membrane phospholipid remodeling by a bacterial Lands cycle phospholipase A is published by Bleffert et al. PlaF dimerization, mediated solely through the intermolecular interactions of TM and juxtamembrane regions, inhibits its activity. (6I8W)

ABHD8

This family was initially included in the Epoxide_hydrolase family but the active site nucleophile is a Serine. The vertebrate proteins present a long desordered N-terminal sequence. Could represent a breast-ovarian cancer susceptibility locus.

ABHD10

Abhydrolase domain-containing protein 10, Mycophenolic acid acyl-glucuronide esterase, mitochondrial. Mycophenolic acid (MPA), the active metabolite of the immunosuppressant mycophenolate mofetil (MMF), is primarily metabolized by glucuronidation to a phenolic glucuronide (MPAG) and an acyl glucuronide (AcMPAG Mycophenolic-acid-acyl-glucuronide). AcMPAG, may be an immunotoxic, and is deglucuronidated by ABBHD10. ABHD10 is an S-depalmitoylase affecting redox homeostasis through peroxiredoxin-5 (Cao et al.). The name of this family should not be confounded with family Abhydrolase_10 which is quite far related and contains only sequences from bacteria and fungi

ABHD11-Acetyl_transferase

ABHD11 is located in the Williams-Beuren syndrome (WBS) critical region. WBS results from a hemizygous deletion of several genes on chromosome 7q11.23, thought to arise as a consequence of unequal crossing over between highly homologous low-copy repeat sequences flanking the deleted region. ABHD11 is an enzyme acting on triacylglycerol. Many yeasts are able to produce ethyl acetate. Enzyme Eat1 from the yeast Wickerhamomyces anomalus showed alcohol acetyltransferase activity with ethanol and acetyl-CoA. Homologs of eat1 are responsible for most ethyl acetate synthesis in known ethyl acetate-producing yeasts, including S. cerevisiae, and are only distantly related to known alcohol acetyltransferases. Structure of ybfF protein from Escherichia coli (esterase of the large substrates, palmitoyl coenzyme A and malonyl coenzyme A) has been solved. Liu et al. published that: ABHD11 is critical for embryonic stem cell expansion, differentiation and lipid metabolic homeostasis

ABHD12-PHARC

Monoacylglycerol lipase protein ABHD12 (also known as the abhydrolase domain-containing protein 12) has 2-arachidonoylglycerol hydrolase activity (Blankman et al. 2007). In humans, defects in ABHD12 are the cause of polyneuropathy hearing loss ataxia retinitis pigmentosa and cataract (PHARC). PHARC is a slowly progressive neurologic disorder (Fiskerstrand 2010). ABHD12 is a major very long chain lyso-PS lipase in primary mast cells. long-chain lyso-PSs induce secretion of pro-inflammatory cytokines in macrophage signaling and mast cell degranulation (Khandelwal 2021)

ABHD13-BEM46

This family is derived from LYsophospholipase_carboxylesterase. It contains animal ABHD13, WAV2 (WAVY GROWTH 2 protein modulates root bending in response to environmental stimuli) of Arabidopsis thaliana, fungal bud emergence 46 (BEM46). BEM46 shows eisosomal localization and association with tryptophan-derived auxin pathway in Neurospora crassa

ABHD16

This family consists of abhydrolase domain-containing protein 16 A (ABHD16A). Function of its members is unknown. However, ABHD16A contains transmembrane domain and is a potential multi-pass membrane protein. BAT5 (HLA-B-associated transcript 5). Savinainen et al. showed hydrolysis of medium-chain saturated (C14:0), long-chain unsaturated (C18:1, C18:2, C20:4) monoacylglycerols (MAGs) and 15-deoxy-12,14-prostaglandin J2-2-glycerol ester (15d-PGJ2-G). Only marginal diacylglycerol (DAG), triacylglycerol (TAG), or lysophospholipase activity PANTHER PTHR12277:SF54 There are two genes ABHD16 A and B in amniotes. Shan et al. identified a nonsense mutation in the bovine ABHD16B associated with male subfertility in Holstein cattle. ABHD16B is involved in lipid biosynthesis in testis and is crucial for fertilization. ABHD16A deficiency causes a complicated form of hereditary spastic paraplegia associated with intellectual disability and cerebral anomalies (Lemire et al. 2021; Yahia et al. 2021; Miyake 2021)

ABHD17-depalmitoylase

ABHD17 proteins are protein depalmitoylases that regulate N-Ras palmitate turnover and subcellular localization (Lin and Conibear 2015) They are probably themselves palmitoylated. ABHD17A, 17B, and 17C, are identified as the physiological PSD-95 (the most abundant postsynaptic density scaffolding protein) depalmitoylating enzymes in neurones (Yokoi et al.). The acyl protein thioesterases (APT1:LYPLA1, APT2: LYPLA2) are G protein depalmitoylases and accept also a number of S-palmitoylated protein and phospholipid substrates. They belong to a closely related family: LYsophospholipase_carboxylesterase

ABHD18

Abhydrolase domain containing 18 (Old Duf_2048 DUF2048). This family of proteins is conserved from plants to humans. The function is unknown.

Abhydrolase_5

This family corresponds partially to PF12695 (Abhydrolase_5), however as previously separated families existed this family does not includes epoxide hyrolase like families which are closely related to this family

Abhydrolase_6

This family has many children sub-families. This family corresponds partially to PF12697 (Abhydrolase_6). However as previously separated families existed this family does not includes epoxide hyrolase like families which are closely related to this family. It also contains families that have their own Pfam entries but are closely related to this subset of the database

Abhydrolase_7

Some members are close to Acetyl-esterase_deacetylase or Dienelactone_hydrolase. Family includes SusD/RagB-associated esterase-like protein (YP_001301335.1) from Bacteroides vulgatus and putative acetyl xylan esterase (BF1801) from Bacteroides fragilis. Previously ProteinCluster-CLSK833894

Abhydrolase_9

Novel transmembrane lipases of alpha/beta hydrolase fold.(Lazniewski et al.) PF10081 Abhydrolase_9 IPR009199 (Old Duf_2319 DUF2319) Uncharacterised conserved protein Alpha/beta-hydrolase_fam UCP007542 PIRSF007542

Abhydrolase_10

Proteins of bacteria and fungi or uncategorised eukaryotes but not in animals or plants. The only sequence of viridi planta (Ricinus communis) might result from an horizontal transfer or a contamination. Although proteins in this family are uncharacterised they are likely to have an enzymatic activity. In mycpa-q73tu8 Mycobacterium paratuberculosis the catalytic triad would be Ser191, Asp259, His 289. The name of this family comes from Pfam but should not be confounded with family ABHD10 which is quite far related

Abhydr_predicted

PIRSF037445 (UCP037445_abhydr) Alpha/beta hydrolase, predicted (IPR017209)

abh_upf0017

This family includes: Escherichia coli yheT (Zhang eta al. 1998); Yeast YBR177c (octanoyl-CoA:ethanol acyltransferase thioesterase), YMR210w, YPL095c; Mammalian ABHD1/2/3/15 are included. Human protein ABHD1, ABHD2 (pHPS1-2), ABHD3, ABHD15 (an essential component in the development of adipocytes as well as in apoptosis Walenta et al. 2013) Human ABHD3 is a phospholipase that may play a role in phospholipids remodeling. It may selectively cleave myristate (C14)-containing phosphatidylcholines through its predominant phospholipase 1 activity, cleaving preferentially acyl groups in sn1 position; Enhanced neointimal hyperplasia was observed in Abhd2-deficient mice, using an experimental vascular cuff placement injury model. Abhd2 is expressed in vascular smooth muscle cells (SMCs). An association between the human ABHD2 gene and colorectal cancer and with Risks for Chronic Obstructive Pulmonary Diseaseis reported. ABHD2 is involved in virus propagation, immune response, and fertilization namely in the P4-stimulated acrosome reaction. Monoacylglycerol lipase ABHD2 is a steroid-activated (progesterone P4) enzyme that hydrolyzes 2-arachidonoylglycerol. ABHD2 is expressed in sperm and in ovaries. ABHD2 regulates the rhythm of follicular maturation and estrous stages of the female reproductive cycle (Bjorkgren et al.) The family also contains: Drosophila protein ABHD2 anon-23D; Picea glauca (white spruce) late embryogenesis abundant protein EMB8 (Dong et al. 1999); and Caenorhabditis elegans C44C1.5. (UPF0017_hydro-like_CS abh_upf0017 IPR000952 (conserved site) is included in IPR012020 Hydrolase_YheT in Interpro. ABHD15 does not have a serine in the position of the catalytic triad. TAMRA-FP probe does not interact with ABHD15. ABHD15 has no hydrolase activity. (These entries where previously included in AlphaBeta_hydrolase family in ESTHER)

abh_upf00227

Despite being classified as uncharacterised proteins, the members of this family are almost certainly enzymes that are distantly related to the abhydrolase. One of the members of this family YqiA has been shown to be a esterase Kuznetsova et al. Other members, which include the Escherichia coli (strain K12) YcfP protein are uncharacterised

Acetyl-esterase_deacetylase

PF05448 AXE1 Acetyl xylan esterase (EC 3.1.1.72) and cephalosporin c deacetylase (EC 3.1.1.41). This domain can be found in several bacterial acetyl xylan esterase proteins. Acetyl xylan esterases are enzymes that hydrolyse the ester linkages of the acetyl groups in position 2 and/or 3 of the xylose moieties of natural acetylated xylan from hardwood. These enzymes are one of the accessory enzymes which are part of the xylanolytic system, together with xylanases, beta-xylosidases, alpha-arabinofuranosidases and methylglucuronidases; these are all required for the complete hydrolysis of xylan Some sequences were previously in the Bacterial_lipase family (thema-TM0077...). Members of the family were associated with IPR000734, the esterase and lipase active site serine. This family contains the carbohydrate esterase family seven (CE-7) see the CAZy (Carbohydrate-Active enZYmes server ) (CE_7)

Acetylxylan_esterase

PF01083 Contains the Acetylxylan_esterase and the Cutinase families as does the cutinase like family in SCOP. This family corresponds to the Carbohydrate Esterase family CE5 in CAZy - Carbohydrate-Active enZYmes database (CE_5)

Acidic_Lipase

This entry represents a family of eukaryotic lipases, including gastric triacylglycerol lipase (LIPF) lysosomal acid lipase (LIPA) and LIPJ, LIPK, LIPM, LIPN. Mutations in LIPA cause Wolman disease, Cholesterol Ester Storage Disease, CESD and mutation in LIPN causes Late-Onset Form of Autosomal-Recessive Congenital Ichthyosis

Aclacinomycin-methylesterase_RdmC

PIRSF037216 Aclacinomycin methylesterase (RdmC) is one of the tailoring enzymes that modify the aklavinone skeleton in the biosynthesis of anthracyclines in Streptomyces species

AcoC_BiotinLipoyl-ABH

This family groups proteins with an architecture composed of two or three domains: a Biotin_lipoyl domain, possibly a E3_binding domain and an alpha/beta hydrolase domain. PF00364. Biotin_lipoyl IPR000089. Biotin_lipoyl. Biotin/lipoyl attachment domain has a conserved lysine residue that binds biotin or lipoic acid. Biotin plays a catalytic role in some carboxyl transfer reactions and is covalently attached, via an amide bond, to a lysine residue in enzymes requiring this coenzyme. PF02817. E3_binding. IPR004167. E3-bd. is a small domain of the E2 subunit of 2-oxo-acid dehydrogenases (not an alpha beta hydrolase) that is responsible for the binding of the E3 subunit. Here dihydrolipoamide acetyltransferase (acoC) from the 2,3-butanediol catabolic pathway: acetyl-CoA:enzyme N6-(dihydrolipoyl)lysine S-acetyltransferase. Transfer of thio acetate from Acetyl-CoA to N6-(dihydrolipoyl)lysine of an enzyme

ACPH_Peptidase_S9

Merops Subfamily S9C. Acylamino-acid-releasing enzyme ACPH APEH. This enzyme catalyzes the hydrolysis of the N-terminal peptide bond of an N-acetylated peptide to generate an N-acetylated amino acid and a peptide with a free N-terminus. It preferentially cleaves off Ac-Ala, Ac-Met and Ac-Ser

Acyl-CoA_Thioesterase

Acyl-CoA thioester hydrolase/bile acid-CoA amino acid N-acetyltransferase. Long chain acyl CoA thioesterases hydrolyze long chain acyl-CoAs to the corresponding free fatty acid and CoASH. The major solutes in bile are N-acyl conjugates of cholanoates (C24 bile acids) with glycine or taurine. These bile acid-amino acid conjugates serve as detergents in the gastrointestinal tract. Bile acid-amino acid conjugates are formed in the liver via a 2-step pathway. The first reaction converts a bile acid to an acyl-CoA thioester and is catalyzed by the microsomal enzyme, cholyl-CoA synthetase (EC 6.2.1.7). The second reaction transfers the bile acid moiety from the acyl-CoA thioester to either glycine or taurine, and is catalyzed by bile acid-CoA:amino acid N-acyltransferase (BAAT; EC 2.3.1.65). Some homologies to Dienelactone_hydrolase and AlphaBeta-hydrolases (PF08840 BAAT only C-term PIRSF019303) The mouse ACOT gene cluster comprises six genes with localizations in cytosol (ACOT1), mitochondria (ACOT2), and peroxisomes (ACOT3-6). The corresponding human gene cluster contains only three genes (ACOT1, ACOT2, and ACOT4) coding for full-length thioesterase proteins only ACOT4 is peroxisomal.Family TE2 in ThYme database

AHL-acylase

Bacterial AHL-acylases (acyl homoserine lactonase) (AiiO, AidH) from genus Ochrobactrum and related bacteria are different from previously described AHL-acylases such as PvdQ, QuiP (P.aeriginosa) HacA HacB (P.syringea which belong to Ntn-hydrolase superfamily Czajkowski et al.) and different from AHL-lactonase of B. thuringensis and A. tumefasciens (which are metallo-beta lactamases). AHL-acylase inactivates N-acyl homoserine lactone (AHL) quorum sensing signal molecules (lactonases are also inactivating enzymes). AHL-acylases could be useful for the control of development of infections caused by pathogenic bacteria and their persistence in respective hosts. The three fungi sequences are genes without real introns (horizontal transfer?). There are other N-acyl homoserine lactonase (AiiA) not alpha/beta hydroalses but Metallo-B-lactamases

AlphaBeta_hydrolase

Contains mostly miscellaneous genes:proteins. Contains entries not included in better characterized families

Antigen85c

This family contains EC 3.1.2.12, human Esterase D and bacterial S-formylglutathione hydrolase. A universal pathway for formaldehyde detoxification. It also contains Antigen85c responsible for high affinity of mycobacteria to fibronectin. This family contains enterobactin, enterochelin enterobactin and salmochelin siderophore esterases also (IroD FES IroE). It also contains enzymes with acetyl xylan esterase (EC 3.1.1.72); cinnamoyl esterase (EC 3.1.1.-); feruloyl esterase (EC 3.1.1.73) activities corresponding to a subset of the Carbohydrate Esterase family CE1 in CAZy - Carbohydrate-Active enZYmes database (CE_1)

Arb2

This domain is found at the C-terminal of Clr3 (Cryptic loci regulator 3) also known as histone deacetylase clr3 (EC:3.5.1.98). Structure analysis reveals that the Arb2 domain has clear homology to alpha/beta-hydrolases but that it is lacking the catalytic triad of these enzymes. Structural and histone binding ability characterization of the ARB2 domain of a histone deacetylase Hda1 from Saccharomyces cerevisiae was published (Shen et al.) and from Saccharomyces pombe (Job et al.) . FAM172A plays an important role in the regulation of cotranscriptional alternative splicing by interacting with Ago2 (Argonaute-2) and Chd7. The FAM172A mutant mice display a complex phenotype mimicking both the major and minor features of CHARGE syndrome (Belanger et al.)

Arb2_domain

This domain is found at the C-terminal of Clr3 (Cryptic loci regulator 3) also known as histone deacetylase clr3 (EC:3.5.1.98). Structure analysis reveals that the Arb2 domain has clear homology to alpha/beta-hydrolases but that it is lacking the catalytic triad of these enzymes. Structural and histone binding ability characterization of the ARB2 domain of a histone deacetylase Hda1 from Saccharomyces cerevisiae was published (Shen et al.) and from Saccharomyces pombe (Job et al.)

Arb2_FAM172A

FAM172A plays an important role in the regulation of cotranscriptional alternative splicing by interacting with Ago2 (Argonaute-2) and Chd7. The FAM172A mutant mice display a complex phenotype mimicking both the major and minor features of CHARGE syndrome (Belanger et al.).

Asp2

(from Interpro) Accessory Sec protein Asp2. Proteins in this entry form part of an accessory Sec system which is involved in the export of serine-rich repeat (SRR) glycoproteins important for virulence in a number of Gram-positive species, including Streptococcus gordonii and Staphylococcus aureus. Asp2 and Asp3 interact directly with GspB and may function in part as chaperones in the early phase of GspB transport. Asp2 is a bifunctional protein that is essential for both GspB transport and correct glycosylation

Atu1826-like

Small bacterial alpha/beta hydrolases PIRSF019303 uncharacterized conserved protein

Bacillus_lip

This family has been recognized as alpha/beta hydrolase by Siew et al. PIRSF021323 Bacillus subtilis hypothetical protein YjaU

Bacterial_Est97

Family XVI was introduced by Fu et al. (2013) The prototype enzyme from this family cold-adapted esterase from an Arctic intertidal metagenomic library. This family is far related to DUF1100 Monoglyceridelipase_lysophospholip and could be separated from Abhydrolase_5

Bacterial_esterase

Members belong either to Abhydrolase_6 or Abhydrolase_5 of pfam database. A novel bacterial esterase that cleaves esters on halogenated cyclic compounds has been isolated from an Alcaligenes species. It is proposed that completion of a functional active site requires the formation of the disulphide bond between adjacent residues Cys71 and Cys72 on export of the esterase into the oxidising environment of the periplasmic space.

Bacterial_EstLip_FamX

Family of Bacterial lipolytic enzymes. Thermotoga maritima conserved Thermostable Esterase EstD is the first characterized member of this family (thema-TM0336) Levisson et al. 2007 (Family 10 Arpigny and Jaeger 1999)

Bacterial_lip_FamI.8

This family correspond to family I.8 of the classification of Arpigny and Jaeger (1999). These lipases differ from other bacterial lipases but groups putative psychrophilic esterases/lipases. The closest family is CarbLipBact_2. Features of the new family include: a conserved new active-site pentapeptide motif (LGG(F/L/Y)STG); the likely extra-cytoplasmic localization; the absence of a typical calcium-binding pocket; and the absence of a canonical lid.

Bact_LipEH166_FamXII

Novel cold-adapted alkaline lipase from an intertidal flat metagenome Kim et al. 2009. Related to Abhydrolase_5 or Lipase_2. Some enzymes contain an extra domain in N- or C-terminal: Bacterial Ig-like domain (group 2)

BioH

Pimelyl-[acyl-carrier protein] methyl ester esterase: BioH family previously included in AlphaBeta_hydrolase family. The structure of ecoli-bioh by Sanishvili et al pdb:1M33 allowed description of function of this family. This CoA-binding enzyme is required for the production of pimeloyl-coenzyme A, the substrate of the BioF protein early in the biosynthesis of biotin. Its exact function is unknown. Members of this family are restricted to the proteobacteria. BioH shows carboxylesterase activity with a preference for short chain fatty acid esters (acyl chain length of up to 6 carbons). It also displays a weak thioesterase activity. Biotin synthesis necessitate the fatty acid synthetic pathway: Malonyl-thioester is methylated by BioC, which allows recognition of this atypical substrate by the fatty acid synthetic enzymes. The malonyl-thioester methyl ester enters fatty acid synthesis as the primer and undergoes two reiterations of the fatty acid elongation cycle to give pimeloyl-acyl carrier protein (ACP) methyl ester, which is hydrolyzed to pimeloyl-ACP and methanol by BioH. In Pseudomonas aeruginosa the bioH gene is within a biotin synthesis operon and its transcription is coregulated with the other biotin operon genes. In Escherichia coli the gene is not located within a biotin synthetic operon and its transcription is not coregulated with the other biotin synthesis genes (Cao et al. 2017). In Francisella BioJ is the enzyme of the biotin biosynthesis pathway that determines the chain length of the biotin valeryl side-chain. It is the functionnal equivalent of BioH although it shows low homology to BioH (belongs to hormone sensitive lipase family)( Feng et al. 2014).In Haemophilus influenzae it is another family Duf_452 which plays the role (Shi et al. 2016). In Helicobacter it is another alpha/beta hydrolase BioV (Bi et al. 2016)

BlEst2-lipase-like

The first structure of Bacillus licheniformis lipase BlEst2 in its propeptide and mature form revealing molecular details of inhibition by its C-terminal domains: Nakamura, A.M., Godoy, A.S., Kadowaki, M.A.S., Polikarpov, I.

Bodyguard

The epidermis-specific extracellular BODYGUARD controls cuticle development and morphogenesis. Only found in plants yet

BotH

The bottromycin epimerase BotH defines a group of atypical alpha/beta-hydrolase-fold enzymes. BotH is a peptide epimerase responsible for the post-translational epimerization of L-Asp to D-Asp during bottromycin biosynthesis. D-amino acids endow peptides with diverse, desirable properties, but the post-translational and site-specific epimerization of L-amino acids into their D-counterparts is rare and chemically challenging. The activity does not rely on a catalytic triad. No conservation of Ser (replaced by Phe) nor His or Asp. The residues Phe110 and Val41 seem important in hydrogen bonding to substrate

CarbLipBact_1

PIRSF017388 Members of this group are esterases, lipases, and (possibly) other hydrolases of the alpha/beta hydrolase fold. The Bacillus stearothermophilus member, Est, has been characterized as a carboxylesterase (EC 3.1.1.1) involved in the detoxification of xenobiotics, and the Bacillus sp. member has been characterized as monoacylglycerol lipase. This family correspond to family XIII of the classification of Arpigny and Jaeger 1999. Family XIII was introduced by Ewis et al.(2004) and Liu et al. (2004). The closest family is Monoglyceridelipase_lysophospholip. The family XIII contains LipS Chow et al.. This family is composed of two sub families with different set of salt-bridges important for thermostability Charbonneau et al. (due to simultaneous publication of new families this family was numbered XV but really is a subset of familly XIII. See notice of this paper in Plos One)

CarbLipBact_2

PIRSF017388 Members of this group are esterases, lipases, and (possibly) other hydrolases of the alpha/beta hydrolase fold. The Bacillus stearothermophilus member, Est, has been characterized as a carboxylesterase (EC 3.1.1.1) involved in the detoxification of xenobiotics, and the Bacillus sp. member has been characterized as monoacylglycerol lipase. This family correspond to family XIII of the classification of Arpigny and Jaeger 1999. Family XIII was introduced by Ewis et al.(2004) and Liu et al. (2004). The closest family is Monoglyceridelipase_lysophospholip. The family XIII contains LipS Chow et al.. This family is composed of two sub families with different set of salt-bridges important for thermostability Charbonneau et al. (due to simultaneous publication of new families this family was numbered XV but really is a subset of familly XIII. See notice of this paper in Plos One)

Carbon-carbon_bond_hydrolase

2-hydroxymuconic semialdehyde hydrolase PIRSF037174. Members of this family are 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoate hydrolase, or HOPD hydrolase, the BphD protein of biphenyl degradation. BphD acts on the product of ring meta-cleavage by BphC. Many species carrying bphC and bphD are capable of degrading polychlorinated biphenyls as well as biphenyl itself (environmental pollutants: BP/PCB). 2-hydroxy-6-oxononadienedioate/2-hydroxy-6-oxononatrienedioate hydrolase catalyzes the cleavage of the C5-C6 bond of 2-hydroxy-6-oxononadienedioate and 2-hydroxy-6-oxononatrienedioate, a dienol ring fission product of the bacterial meta-cleavage pathway for degradation of phenylpropionic acid. The purified enzyme is a dimeric protein requiring no cofactors for catalytic activity

Carboxymethylbutenolide_lactonase

In some instance 3-oxoadipate enol-lactonase is fused to 4-carboxymucolactone- decarboxylase, which acts on the same pathway but this enzyme belongs to CMD IPR003779 PF02627 and is not related to alpha/beta hydrolase see Eulberg et al. 1998, see Schlomann et al. 1994 fo a review on the pathway. For bacterial enzymes, this family corresponds to family V.2 of the classification of Arpigny and Jaeger 1999

Carboxypeptidase_S10

Serine carboxypeptidase-like (SCPL) proteins. Structures determined for wheat and yeast peptidase first. Very successful family in plants (arabdopsis) also human protective protein cathepsineA. The protective protein human-CTSA is a glycoprotein that associates with lysosomal beta-galactosidase and neuraminidase and is deficient in the autosomal recessive disorder Galactosialidosis . Also contains non peptidase sequences as hydroxynitril lyase from plants. But new structure of sorghum hnl shows clear differences in catalytic mechanism because of a deletion of two amino acid adjescent of the active site serine: see sorbi-hnl and 1GXS Lauble et al 2002. It does not accept aliphatic hydroxynitriles, unlike EC 4.1.2.10 mandelonitrile lyase and EC 4.1.2.39 hydroxynitrilase. Other hydroxynitril lyase belong to another family: Hydroxynitrile_lyase . This Carboxypeptidase family also contains acyltransferases as sinapoyltransferase AT2G22990 arath-SCP8 SNG1 gene. Another enzyme, related to the SCPL family, is glucose acyltransferase from Lycopersicon pennellii catalysing the formation of diacylglucose

CFTR-inhibitory-factor_Cif

The Gram-negative bacterium Pseudomonas aeruginosa is an opportunistic pathogen that secretes a multitude of virulence factors during the course of infection. Among these is Cif, an epoxide hydrolase (EH) that reduces the functional localization of the cystic fibrosis transmembrane conductance regulator in epithelial cells. In contrast with other EH, it shows a subtitution of an histidine for the second epoxide ring-opening tyrosine in the active site. We used the site around the H177 of the lid defined by Bahl and Madden to build this family: [ED]-X(3)-P-X(13,18)-W-H-[FIA]-X-[FYL]-X(4,7)-[ELT]-X(4)-[GD NAK]-X-[VPE]-X(2)-[FYL]-[LVFI]

CGI-58_ABHD5_ABHD4

Comparative gene identification 58 (CGI-58)/Alpha Beta Hydrolase Domain 5 (ABHD5) NCIE2 functions as an acyltransferase for the synthesis of phosphatidic acid, the major intermediate in membrane and storage lipid biosynthesis. It also functions as a coactivator of adipocyte triglyceride lipase (ATGL, or PNPLA2) (Ghosh et al., 2008)CGI-58 is regulated by its interaction with perilipin 1 (PLIN1) localized on the lipid droplet (LD), and its release is controlled by phosphorylation. Once lipolysis is stimulated by catecholamines, protein kinase A (PKA)-mediated phosphorylation enables the dissociation of the CGI-58/PLIN1 complex, thereby recruiting adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) to initiate fatty acid release. Mutations in CGI-58 were found in Chanarin-Dorfman syndrome. (from OMIM) By examining the critical region for triglyceride storage disease with impaired long-chain fatty acid oxidation, a rare autosomal recessive form of NCIE (242100), on chromosome 3p21, Lefevre et al.(2001) identified several candidate genes, one of which was designated comparative gene identification-58 (human-ABHD5 ). Lefevre et al. (2001) identified 8 different haplotypes and mutations in the human-ABHD5 gene. The disease locus was designated NCIE2. ABHD5_CGI58 is an activator of the adipose triglyceride lipase (TAG lipase, PNPLA2.patatin-like phospholipase domain-containing). ABHD_ CGI-58 proteins orthologs from plants and yeast are weak triglyceride and phospholipid hydrolases. In plants it interacts with peroxisomal transport protein PXA1. PNPLA3/Adiponutrin and ATGL(PNPLA2 patatin) compete for interaction with ABHD5 (Yang et al.). Comparative gene identification 58 (CGI-58)/Alpha Beta Hydrolase Domain 5 (ABHD5) lacks lysophosphatidic acid acyltransferase activity (McMahon et al.). Disruption of the Arabidopsis CGI-58 homologue produces Chanarin-Dorfman-like lipid droplet accumulation in plants (James et al.).ABHD5 is in fact a protease and hydrolyses HDAC4. Through the production of an amino-terminal polypeptide of HDAC4 (HDAC4-NT) in heart, ABHD5 inhibits MEF2-dependent gene expression and thereby controls glucose handling (Jabessa et al. 2019). Two highly conserved ABHD5 amino acids (R299 and G328) enabled ABHD4 (ABHD4 N303R/S332G) to activate ATGL. The corresponding ABHD5 mutations (ABHD5 R299N and ABHD5 G328S) selectively disrupted lipolysis without affecting ATGL lipid droplet translocation or ABHD5 interactions with perilipin proteins and ABHD5 ligands Sanders et al. In Drosophila Pummelig (Puml,colloquial German for chubby) pummelig deletion mutants (puml1) (Hehlert et al.) Pummelig release fatty acids from phosphatidic acid (PA), N-acylphosphatidylethanolamine (NAPE) and phosphatidylglycerol (PG) but does not hydrolyse TG, diolen or monoolein. Pummelig localizes to lipid droplets, mitochondria, and peroxisomes

CIB-CCG1-interacting-factor-B

Alpha/beta hydrolase domain-containing protein 14B. The general transcription initiation factor TFIID and its interactors play critical roles in regulating the transcription. TFIID interactor CCG1/TAF(II)250-interacting factor B (CIB) activates transcription and has hydrolase activity towards p-nitrophenyl butyrate (in vitro). Dorz1 (ABHD14A,ABHEA) was identified and characterized as one of the most significantly down-regulated genes in Zic1-deficient cerebellum (Zic1: zinc finger protein that controls vertebrate neural development) Crystal structure of predicted CIB-like hydrolase (NP_393672.1) from Thermoplasma acidophilum has also been released. ABHD14B is able to transfer an acetyl group from a post-translationally acetylated-lysine to coenzyme A (CoA) and yield acetyl-CoA, while re-generating the free amine of protein lysine residues (Rajendran et al. 2019): lysine deacetylase (Previously IPR026764 Alpha/beta hydrolase domain containing protein 14B)

CMBL

(from Interpro) Carboxymethylenebutenolidase (CMBL) is a human homologue of Pseudomonas dienelactone hydrolase involved in the bacterial halocatechol degradation pathway. It is a cysteine hydrolase that can convert the prodrug olmesartan medoxomil into its pharmacologically active metabolite olmerstatan, an angiotensin receptor blocker, in liver and intestine. May also activate beta-lactam antibiotics faropenem medoxomil and lenampicillin. Not inhibited by DFP, PMSF, eserine or EDTA. Strongly inhibited by p-chloromercuribenzoate (PCMB). This entry also includes uncharacterised DLH domain-containing proteins from plants. This family was previously included in Dienelactone_hydrolase

Cocaine_esterase

Contains also alpha-amino acid ester hydrolase (Beta-Lactam Acylase), glutaryl 7-aca acylases, antibiotic hydrolase, diester hydrolase. Able to perform both hydrolysis and synthesis of a variety of -amino -lactam antibiotics including (R)-ampicillin and cephalexin. The closest relatives is the S15 X-prolyl amino peptidase of Lactobacillus

Cutinase

This family corresponds to the Carbohydrate Esterase family CE5 in CAZy - Carbohydrate-Active enZYmes database (CE_5). (from interpro) Aerial plant organs are protected by a cuticle composed of an insoluble polymeric structural compound, cutin, which is a polyester composed of hydroxy and hydroxyepoxy fatty acids. Plant pathogenic fungi produce extracellular degradative enzymes that play an important role in pathogenesis. They include cutinase, which hydrolyses cutin, facilitating fungus penetration through the cuticle. Inhibition of the enzyme can prevent fungal infection through intact cuticles. Cutin monomers released from the cuticle by small amounts of cutinase on fungal spore surfaces can greatly increase the amount of cutinase secreted by the spore, the mechanism for which process is as yet unknown. It is shown by Masaki et al. that some Cutinase-Like enzyme hydrolyzes polylactic acid and other biodegradable plastics

Cutinase_like

This family corresponds to the Carbohydrate Esterase family CE5 in CAZy - Carbohydrate-Active enZYmes database (CE_5) (from interpro) Aerial plant organs are protected by a cuticle composed of an insoluble polymeric structural compound, cutin, which is a polyester composed of hydroxy and hydroxyepoxy fatty acids. Plant pathogenic fungi produce extracellular degradative enzymes that play an important role in pathogenesis. They include cutinase, which hydrolyses cutin, facilitating fungus penetration through the cuticle. Inhibition of the enzyme can prevent fungal infection through intact cuticles.

Dieckmann_Cyclase

Off-loading Dieckmann cyclase, NcmC, that installs the tetramate head group in nocamycin, a hybrid polyketide/nonribosomalpeptide natural product. A conserved thioesterase-like scaffold has been adapted to perform a new chemical reaction: heterocyclization. The catalytic triad for the cyclization reaction consists of Cys89, Asp116, and His254 in 9pseu-NcmC. Dieckmann cyclase (TrdC, SlgL, LipX2, KirHI,and FacH) last step which generate actinomycete-derived tetramic acid and pyridone natural products in the biosynthetic pathways for Tirandamycin, Streptolydigin, alpha-Lipomycin, Kirromycin, and Factumycin

Dienelactone_hydrolase

Dienelactone hydrolases play a crucial role in chlorocatechol degradation via the modified ortho cleavage pathway. Enzymes induced in 4-fluorobenzoate-utilizing bacteria have been classified into three groups on the basis of their specificity towards cis- and trans-dienelactone. The catalytic triad of the prototype psepu-clcd1 consists of Cys123, His202 and Asp171

DLH-S

Members of this family often annotated as Dienelactone hydrolases. However there are not many experimental data to support this. Although this family is distantly related to DLH, members have generaly a Serine instead of a cysteine in the position of the active site nucleophile residue as in DLH. The domain is found often in c-terminal of Phosphoribosyl transferase domain Pribosyltran (PF00156)

DPP4N_Peptidase_S9

Dipeptidyl petidase IV related proteins (EC 3.4.14.5) (DPP IV) important for the activation or inactivation of extracellular endocrine paracrine and autocrine peptides. DPPIV is synonymous with CD26 (important in HIV infection). Some members lack active serine and are probably not enzymes. The prototype structure has a 8-bladed beta-propeller N-terminal domain which guide substrates to the active site and a transmembrane segment. DPP4 is a cell surface glycoprotein receptor involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation. Acts as a positive regulator of T-cell coactivation, by binding at least ADA, CAV1, IGF2R, and PTPRC. Its binding to CAV1 and CARD11 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner. Its interaction with ADA also regulates lymphocyte-epithelial cell adhesion. In association with FAP is involved in the pericellular proteolysis of the extracellular matrix (ECM), the migration and invasion of endothelial cells into the ECM. May be involved in the promotion of lymphatic endothelial cells adhesion, migration and tube formation. The novel emerging coronavirus Middle East respiratory syndrome coronavirus (MERS-CoV) binds cells through DPP4. Mutations in the DPP6 gene are linked to autosomal dominant mental retardation.(Liao et al 2013). The dipeptidyl-aminopeptidase-like protein 6 is an integral voltage sensor-interacting beta-subunit of neuronal K(V)4.2 channels. Structures of the complex are available (Kise et al.)

Duf_452

IPR007398 Proteins all bacterian of unknown function DUF452. Haemophilus influenzae pimeloyl-acyl carrier protein (ACP) methyl esterase BioG that lack significant sequence identity with other isofunctional forms of this enzyme found in other bacteria (e.g. Escherichia coli BioH or Helicobacter pylori BioV) Shi et al.

Duf_676

This family is made up of a group of uncharacterised eukaryotic proteins that are distantly related to the abhydrolase. It contains IPR016445 Rog1 is a yeast monoacylglycerol (MAG) lipase Lipase and the paralogue YDL109c phospholipase Lpl1. PIRSF005412 UCP005412_abhydr. Selvaraju et al. identified a phospholipase B encoded by the LPL1 gene in Saccharomyces cerevisiae which belongs to this family. In animals the protein is very long. Only c-term is Duf_676 In human the protein is called family with sequence similarity 135 member A F135A

Duf_726

A lipase like protein: yeast-yfd4 Mil1(Yfl034w) specifically binds Apm2, one of the adaptor protein of (AP) complexes responsible for binding clathrin, cargo-sorting motifs, accessory factors, and membrane lipids. The paper by Whitfield et al. is the first description of a function for a member of the Duf_726 family. The same protein had been shown to interact with the ribosomal phosphoprotein P0 Aruna et al.. yeast-yfd4 has a conserved catalytic triad. This family consists of several uncharacterised eukaryotic proteins.

Duf_818

This family consists of several Chlamydia and Parachlamydia proteins, the function of which are unknown.

Duf_829

Protein of unknown function DUF829. Contains exclusively eukaryote proteins including transmembrane protein 53. Said to be integral membrane proteins (!?) Dictyostelium discoideum Net4 (dicdi-q54yr8), which has strong homologies to mammalian DUF829/Tmem53/NET4 is found on lipid droplets (Du et al.). Seems to have a conserved catalytic triad Ser-113, Asp-220, and His-252 in TMEM53_HUMAN

Duf_900

This family consists of several hypothetical proteins of unknown function mostly found in Rhizobium species. Members of this family have an alpha/beta hydrolase fold.

Duf_915

Bacterial protein of unknown function DUF915

Duf_1023

This family has been recognized as alpha/beta hydrolase by Zheng et al. . Pfam family DUF1023 consists entirely of uncharacterized proteins generated by sequencing the genomes of Actinobacteria (Zheng et al 2005) Genomic context suggests that they may function as lipases, controlling the concentration of their putative phospholipid substrates. Most sequences include long n-terminal low complexity region not included here

Duf_1057

IPR010463 DUF1057_lipase. This family consists of several nematodes ( first seen in Caenorhabditis elegans) specific proteins of unknown function. Members of this family have an alpha/beta hydrolase fold.

Duf_1100-R

DUF1100 UPF0255. The family was split in two. Duf_1100-S with active site (S217 in (GXSXG) D300 H329) as in artni-Q93NG6, and Duf_1100-R with active site (R53, D203, R 272 (in GXRXG)) as in FrsA. The fermentation/respiration switch protein FrsA (product of the yafA gene in E. Coli (ecoli-yafa)(vibvy-y856) binds the dephosphorylated form of glucose-specific enzyme IIAGl the interaction increases the glucose fermentation under oxygen-limited conditions. FrsA is a pyruvate decarboxylase (Lee et al.)(In Scop 2,6-dihydropseudooxynicotine hydrolase) Thus there are two functions and two different active sites in this family (nucleophile elbow: GXSXG in hydrolase, GXRXG in decarboxylase). However (Kellett et al.) showed Computational, structural, and kinetic evidence that Vibrio vulnificus FrsA is not a cofactor-independent pyruvate decarboxylase. Other members of this family are still uncharacterised

Duf_1100-S

DUF1100 UPF0255. The family was split in two. Duf_1100-S with active site (S217 in (GXSXG) D300 H329) as in artni-Q93NG6, and Duf_1100-R with active site (R53, D203, R 272 (in GXRXG)) as in FrsA. This family is represented by a C-C bond cleaving alpha/beta-hydrolase involved in nicotine degradation: 2,6-dihydroxy-pseudo-oxynicotine hydrolase from the nicotine-degradation pathway of Arthrobacter nicotinovorans (artni-Q93NG6a) (Schleberger et al.). The family also includes the hydrolytic polyketide shortening protein Ayg1 from fungi (Fujii et al.), and Fus2 from Gibberella species, which is part of the gene cluster that mediates the biosynthesis of the mycotoxin fusarin C. Fus2 catalyses closure of the 2-pyrrolidone ring of the intermediate 20-hydroxy-prefusarin to form another intermediate, 20-hydroxy-fusarin, which is then oxidized by Fus8 (Niehaus et al.). Other members of this family are still uncharacterised

Duf_1350

This family consists of several hypothetical proteins from both cyanobacteria and plants. Members of this family are typically around 250 residues in length. The function of this family is unknown but the species distribution indicates that the family may be involved in photosynthesis.

Duf_1400

IPR010802; DUF1400_cyn This domain is specific to cyanobacterial proteins, its function and the function of the proteins it is associated with, are uncharacterised. Almost half of the protein with the DUF1400 domain are not associated with an alpha beta hydrolase domain. They are not accounted for in ESTHER. Here the DUF1400 domain is associated with mostly with Chlorophyllase or PAF-AH_p_II

Duf_1749

Grundlingern et al. show that Aspergillus fumigatus AFUA_3G03390 gene product, SidJ (aspfu-q4wf56) is involved in hydrolysis of siderophore fusarinine C. It is the first functionally characterized member of the family. Structure of siderophore esterase AfSidJ from Aspergillus fumigatus is described by Ecker et al.. A structure of a protein of unknown fucntion is also available (2Q0X) Merritt et al. . However this protein is only representative of trypanosomatid members of this sequence family as these proteins lack some if not all of the catalytic triad residues. Fusarinine C is an intracellular siderophore (an iron-chelating compound that transports iron across membranes) that is crucial for virulence. The closely related siderophore triacetylfusarinine C is not hydrolysed by SidJ. Homologues of SidJ are found in plants and bacteria. (Not to be cofounded with SidJ Calmodulin-dependent glutamylase from Legionella pneumophila)

Duf_2235

The type VI lipase effectors Tle1-Tle5 secreted by the bacterial type VI secretion system (T6SS) have recently been identified as antibacterial effectors that hydrolyze membrane phospholipids. The Tle1-4 display phospholipase A1 and A2 (PLA1) (PLA2) activities. Tle1 belongs to Duf_2235 family, TLE2 to Lipase_3, TLE3 to alpha/ beta hydrolase and Tle4 belongs to PGAP1. The adjacent genes code for VgrG proteins and putative periplasmic immunity proteins Tle5 are unrelated phospholipase D type. The bacterial type VI secretion system (T6SS) is a macromolecular machine that injects effectors into prokaryotic and eukaryotic cells. In enteroaggregative Escherichia coli, the Tle1 phospholipase binds the C-terminal extension of the VgrG trimeric spike. The inhibition of Tle1 phospholipase activity once bound to VgrG suggests that Tle1 dissociation from VgrG is required upon delivery

Duf_2920

Protein of unknown function DUF2920 (IPR022605) essentially from Campylobacter bacteria

Duf_3089

New lipolytic enzyme family defined from isolation and characterization of two esterases from a metagenomic library Bayer et al. (EstGK1 and EstZ3) Lee et al. (EstD2) (Family XV Arpigny et Jaeger (1999))(Charbonneau et al. had defined a family XV but the enzyme described in this paper is really is a subset of familly XIII. See notice of this paper in Plos One). The enzyme in this family are esterase with maximum activity towards C4 aliphatic chains and undetectable activity towards C10 and longer chains

Duf_3141

Family close to Pha_depolymerase. This family of proteins with unknown function appears to be restricted to Proteobacteria. The only plant sequence could be a contaminant. The only characterized protein is rhime-yack which belongs to an operon inducible by phosphate stress

Duf_3530

This family of proteins is functionally uncharacterised. This protein is found in bacteria. Proteins in this family are typically between 272 to 336 amino acids in length. These proteins are distantly related to alpa/beta hydrolases so they may act as enzymes.

Epoxide-hydrolase_like

This family closely related to Abhydrolase_6 contains previously separated families (in Pfam they are partially included in Abhydrolase_6). In epoxide hydrolase, haloalkane dehalogenase, haloacetate_dehalogenase, the catalytic triad nucleophile is an invariable aspartate. Asp attacks a carbon of the epoxide moiety, opening the ring and forming an ester-linked substrate-enzyme intermediate complex. An activated water molecule, hydrolyzes the ester bond and releases diol as the product of catalysis. Two Tyr residues are located on the opposite side of the active site from the nucleophile. They hydrogen bond with the epoxide oxygen, positioning the substrate in the active site for nucleophilic attack. In Cif one of the Tyr is replaced by His

Epoxide_hydrolase

Epoxide hydrolases catalyze the conversion of epoxides to corresponding diols. The catalytic triad nucleophile is an invariable aspartate that opens the epoxide ring by nuclophile attack. The mammalian soluble EHs contain 2 evolutionarily distinct domains, the N-terminal domain is similar to bacterial haloacid dehalogenase (not related to alpha/beta-hydrolase fold), while the C-terminal domain is similar to soluble plant EH, microsomal EH, and bacterial haloalkane_dehalogenase (HLD). In InterPro IPR000639 groups Epoxide hydrolase and Haloalkane dehalogenase. IPR000639; Epoxide hydrolase contains some Carboxymethylbutenolide_lactonase (trembl Q9WWZ4) Carbon-carbon_bond_hydrolase (trembl Q98I15 Q9KH20 Q9K5C1 Q9KWQ6 Q9ZAY1 Q9ZNJ3 Q9RBF3 Q9RBT0) Monoglyceridelipase_lysophospholip (trembl Q97TG8). In ESTHER they are classified in the later sub family. (there are also epoxide hydrolases not related to a/b hydrolases ex: 1NWW limonene-1,2-epoxide hydrolase Arand et al. 2003) Zhu et al. (2003) identified compound heterozygosity for 2 mutations in the EPHX1 gene, which resulted in a significant decrease in EPHX1 promoter activity.

Est-OsmC

composed of an N-terminal carboxylesterase domain and a C-terminal OsmC-like domain (osmotically induced family of proteins-like domain. This domain is not related to ABHD and excluded here. E.coli OsmC protein is able to metabolise peroxide, but in the Est-OsmC this activity is not found). Members of the family contained a second, less well conserved,GxSxG pentapeptide found 32 residues upstream of the completely conserved pentapeptide containing the active Serine. Two cysteine residues included in a putative substrate-binding region are found in the N-terminus.

Esterase_phb

Esterase, PHB depolymerase bacterial depolymerases for poly(3-hydroxybutyrate) (PHB) and related polyhydroxyalkanoates (PHA), as well as acetyl xylan esterases, and feruloyl esterases from fungi.TIGR01840 esterase_phb. This family is included in the Carbohydrate Esterase family CE1 in CAZy - Carbohydrate-Active enZYmes database (CE_1)

Esterase_phb_PHAZ

This is a circularly permuted variant of the alpha/beta hydrolase fold. so could be recognised as a subfamily of Esterase_phb (circular permutation: the first 100 residues are found in c-terminus in Esterase phb)

FaeC

(from Interpro) This is a family of type-C feruloyl esterases. Feruloyl esterases catalyze the hydrolysis of the 4-hydroxy-3-methoxycinnamoyl (feruloyl) group from an esterified sugar, which is usually arabinose in 'natural' substrates. FaeC from Aspergillus oryzae and Emericella nidulans have been shown to display hydrolytic activity towards arabinoxylan and methyl ferulate, among other substrates. Many proteins in the family have a Cellulose Binding Motif (CBM) or a Ricin_B_lectin motif shuffled either at N-terminus or C-terminus of the core alpha/beta hydrolase sequence. These have been excluded in the sequences used in alignment and BLAST base. Other less frequent extensions include IPR013784 Carb-bd-like_fold; IPR026444 Secre_tail; IPR008969 CarboxyPept-like_regulatory

FSH1

Family of serine hydrolase 1(FSH1). Previously: Domain of unknown function (DUF341). Contains human-OVCA2 Human Candidate tumor suppressor in ovarian cancer and yeast-FSH3 regulated by the Crt1 transcription factor, an effector of the DNA damage checkpoint pathway in Saccharomyces cerevisiae, may be involved in folate metabolism. Contains also the gene (dfr1) encoding FSH1 linked to a domain corresponding to dihydrofolate reductase (DHFR) in Schizosaccharomyces pombe. Fsh1p was identified as a lysophospholipase that specifically acts on lysophosphatidylserine (LPS) and impacts the lipid homeostasis in S. cerevisiae. Contains also Aspergillus terreus esterase LovG, which catalyzes the release of covalently bound dihydromonacolin L from LovB during lovastatin biosynthesis. OVCA2 has a strong preference for long-chain alkyl ester substrates (>10-carbons) and high selectivity against a variety of short, branched, and substituted esters

Fungal-Bact_LIP

Secretory lipases. Fungal-Bact_LIP is a new family as described by Neugnot et al. and Hube et al. These lipases are expressed and secreted during the infection cycle of these pathogens. In particular, C. albicans has a large number of different lipases, possibly reflecting broad lipolytic activity, which may contribute to the persistence and virulence of C. albicans in human tissue. CalA is highly unusual in that it accepts tertiary alcohols and shows a high selectivity for the N-acylation of beta-amino esters. It has also amidase activity. Bassegoda et al. defined the bacterial members of this family as Family X.2 of Bacterial lipases (Family 10.2 in the updated classification of Arpigny et Jaeger (1999) ). Castilla et al. Defined a new lipase family (Family XVII) (Family 17) with a novel thermophilic and halophilic esterase from Janibacter sp. R02 as the first member of this subfamily. Parapouli et al. analysed a new thermostable alkaliphilic lipase LipSm from Stenotrophomonas maltophilia. These authors created a new family XIX for homologues of this enzyme

Fungal-D14-Strigolactone-R

Strigolactones are endogenous butenolide hormones that regulate shoot and root architecture, and stimulate the branching of arbuscular mycorrhizal fungi. D14 act as component of hormone signaling or as enzymes that participates in the conversion of strigolactones to the bioactive form. The fungi D14 although homologous to RsbQ-like family of plant strigolactone receptors are somewhat far related and cannot rescue lack of receptor in arabidopsis for example

Glucuronoyl_esterase

Glucuronoyl esterase could be important in cleavage of ester bonds between 4-O-methyl-D-glucuronic acid side residues of glucuronoxylans and lignin alcohols and facilitate lignin degradation. This family contains the carbohydrate esterase family 15 (CE-15) see the CAZy (Carbohydrate-Active enZYmes server ) (CE_15)

Glutamyl_Peptidase_S9

A stromal glutamyl endopeptidase (GEP) that can cleave in vitro a short peptide corresponding to the N-terminal part of Lhcb1 (which belongs to the family of chlorophyll a/b binding proteins) was recently found in pea. Not all Glutamyl endopeptidase belong to Alpha/beta Hydrolases ( see glutamic-class prolyl-endopeptidase neprosin). Glutamyl endopeptidase cleaves the synthetic substrate Z-Leu-Leu-Glu-naphthylamide (Yamauchi et al., 2001).

Haloacetate_dehalogenase

As in epoxide hydrolase and haloalkane dehalogenase the catalytic triad nucleophile is an invariable aspartate. The region around the nucleophile aspartate is GHDRG. See van Loo 2006 Appl.Environ.Microbiol 72 2905

Haloalkane_dehalogenase-HLD1

Haloalkane dehalogenases (HLDs) are enzymes that catalyze the cleavage of carbon halogen bonds by a hydrolytic mechanism. The catalytic triad consists of the key nucleophile (Asp) the general base (His) and a catalytic acid (Asp or Glu). HLD where subdivided in three subfamily (Chovancova et al.) according to their substrate specificity and position of active site residues. Class one HLD1 (HLD-I) has catalytic triad Asp-His-Asp and halide-strabilizing residues Trp-Trp. Class two HLDII (HLD-II) has catalytic triad Asp-His-Glu and halide-stabilizing residues Asn-Trp. Class three HLDIII (HLD-III) has catalytic triad Asp-His-Asp and halide-strabilizing residues Asn-Trp. Also the reaction performed is different, the Renilla reniformis luciferase belongs to this family. In ESTHER as in HAMAP database class I and III are merged as they are close. OleB from bacterial hydrocarbon biosynthesis is a -lactone decarboxylase (Christenson et al.2017)

Haloalkane_dehalogenase-HLD2

Haloalkane dehalogenases (HLDs) are enzymes that catalyze the cleavage of carbon halogen bonds by a hydrolytic mechanism. The catalytic triad consists of the key nucleophile (Asp) the general base (His) and a catalytic acid (Asp or Glu). HLD where subdivided in three subfamily (Chovancova et al.) according to their substrate specificity and position of active site residues. Class one HLD1 (HLD-I) has catalytic triad Asp-His-Asp and halide-strabilizing residues Trp-Trp. Class two HLDII (HLD-II) has catalytic triad Asp-His-Glu and halide-stabilizing residues Asn-Trp. Class three HLDIII (HLD-III) has catalytic triad Asp-His-Asp and halide-strabilizing residues Asn-Trp. Although the reaction performed is different the Renilla reniformis luciferase belongs to this family. In ESTHER as in HAMAP database class I and III are merged as they are close. Luciferase from Renilla reniformis (RLuc) catalyzes the degradation of coelenterazine in the presence of molecular oxygen, resulting in the product coelenteramide, carbon dioxide, and the desired photon of light (EC 1.13.12.5). This enzyme belongs to the Haloalkane dehalogenase family II with a different catalytic function (EC 3.8.1.5) (this luciferase is different from fireflies luciferases classified as Luciferin 4-monooxygenase; ATP-dependent AMP-binding enzyme family). Reconstruction of an ancestral enzyme shows it has both hydrolase and monooxygenase activities ( Chaloupkova et al.)

Haloperoxidase

Non-heme Peroxidase. Bacterial and fungi non-heme bromo- and chloro-peroxidases family. Haloperoxidases catalyze the halogenation of organic compounds in the presence of halide ions and peroxides such as H2O2. They are named after the most electronegative halide they are able to oxidize and are classified according to their cofactor dependence as heme-type, vanadium-dependent and metal-free haloperoxidases (WARNING Only metal free haloperoxidases are alpha beta hydrolases with a Ser-His-Asp catalytic triad in the active center. This family contains also homologous arylesterases.)

HNLyase_Bact

This family is close to the Hydroxynitrile_lyase of Plants although not fully characterized yet. The first enzyme studied by Reiter et al. was able to hydrolyze a variety of esterase substrates of low to medium carbonic acid chain length, but no triglycerides were hydrolyzed. Despite the high sequence homology, no hydroxynitrile lyase activity could be recognized. Plant Hydroxynitrile_lyase are grouped in another family. Hydroxynitrile_lyase but are very closely related).Proteins in this entry also include pyrethroids pesticides hydrolase PytH from Sphingobium wenxiniae

HOD-cofactorfree-dioxygenase

1h-3-hydroxy-4-oxoquinaldine 2,4-dioxygenase (HOD) Oxygenases without requirement for cofactors or metal ions, catalyzing N-heterocyclic-ring cleavage and formation of carbon monoxide. Composed of a classical alpha/beta-hydrolase fold core domain with a cap domain. Organic substrates undergo selective deprotonation of their hydroxyl group by a His/Asp charge-relay system affording the generation of electron-donating species. The oxyanion hole of the alpha/beta-hydrolase fold, is utilized here to host and control oxygen chemistry involving a peroxide anion intermediate. Product release occurs by proton back transfer from the catalytic histidine.It is a non-nucleophilic general-base mechanism

Homoserine_transacetylase

Homoserine acetyltransferase (homoserine transacetylase; EC: 2.3.1.31) catalyses the first step unique to methionine biosynthesis, converting L-homoserine to O-acetyl-L-homoserine using acetyl-CoA as an acetyl group donor. This enzyme is unique to fungi and some bacteria. This enzyme regulates homoserine in a number of biosynthetic pathways, making it vital to cell growth and viability. The biosynthesis of methionine in particular has been shown to be susceptible to small-molecule inhibition in fungi and is consequently a good candidate for antifungal agents PIRSF000443. A subset of this family was shown by Toelzer et al. to be esterases and unable to bind acetyl-CoA and was extracted as a new family (Homoserine_transacetylase_like_est)

Homoserine_transacetylase_like_est

Toelzer et al. showed that MekB (9psed-q0mrg5) from Pseudomonas veronii and CgHle (corgl-CGL0839) from Corynebacteriumglutamicum are esterases that hydrolyse preferentially acetic acid esters. MekB and CgHle cannot bind homoserine and acetyl-CoA. Accordingly a novel esterase subfamily was extracted from the Homoserine_transacetylase family

Hydrolase-1_PEP

Hydrolase, ortholog 1, exosortase system type 1 associated. These proteins are generally found in genomes containing the exosortase/PEP-CTERM protein export system, specifically the type 1 variant of this system. When found in this context they are invariably present in the vicinity of a second, relatively unrelated enzyme (orthologue 2, IPR017532) of the same superfamily.

Hydrolase-2_PEP

Hydrolase, ortholog 2, exosortase system type 2 associated. These proteins are generally found in genomes containing the exosortase/PEP-CTERM protein export system, specifically the type 1 variant of this system . When found in this context they are invariably present in the vicinity of a second, relatively unrelated enzyme (orthologue 1, IPR017531) of the same superfamily.

Hydrolase_4

Monoglyceride lipase/lysophospholipase, Mammalian ABHD1/2/3/15 are included. ABHD17 proteins are protein depalmitoylases. ABHD12 Is a Monoacylglycerol lipase protein 2-arachidonoylglycerol hydrolase activity. In humans, defects in ABHD12 are the cause of polyneuropathy hearing loss ataxia retinitis pigmentosa and cataract (PHARC)

Hydrolase_RBBP9_YdeN

Ser_hydrolase.Hydrolase_RBBP9/YdeN . Protein of unknown function DUF1234 (old Duf_1234). This family contains Bacillus subtilis yden protein and human retinoblastoma-binding protein 9 (RBBP-9) required for pancreatic neoplasia. Members of this family have serine hydrolase activity. They contain a conserved serine hydrolase motif, GXSXG/A, where the serine is a putative nucleophile. Eukaryotic members of this family have a conserved LXCXE motif, which binds to retinoblastomas. This motif is absent from prokaryotic members of this family

Hydroxynitrile_lyase

This entry represents a group of alpha/beta-hydrolase fold-containing proteins mostly from plants, including methylesterase (MES) and hydroxynitrile lyase (HNL) from Arabidopsis. (bacterial Hydroxynitrile_lyase are grouped in another family. HNLyase_Bact but are very closely related). There are at least 20 Arabidopsis MES members (AtMES1AtMES20). The catalytic triad Ser-His-Asp is conserved in 15 of these proteins. However, AtMES19 and AtMES20 lack part of the N-terminal or C-terminal region, respectively, and are therefore likely to be inactive enzymes. AtHNL catalyses the cleavage of cyanohydrins to yield hydrocyanic acid (HCN) and the respective carbonyl compound and are key enzymes in the process of cyanogenesis in plants. Interestingly, HNL homologue from Hevea brasiliensis, known as HbHNL, has opposite enantioselectivities and different reaction mechanisms compared to AtHNL Cyanogenesis is a defense process of several thousand plant species. Hydroxynitrile lyase, a key enzyme of this process, cleaves a cyanohydrin into hydrocyanic acid and the corresponding aldehyde or ketone. The reverse reaction constitutes an important tool in biocatalysis. Hydroxynitrile lyase activity is performed by a wide variety of enzymes some resemble carboxypetidase (see sorghum hnl) other have completely unrelated sequences and structure and are more related to FAD-dependent oxidoreductases (GMC oxidoreductases family see structure 1JU2 Dreveny et al Structure 2001 9 803) or Zn dependent alcohol dehydrogenases and bacterial cupins. The present family also contains high affinity salicylic acid-binding protein 2 from plants required for innate immunity. Kumar et al. The structure of Methylketone synthase 1 revealed a new active site for an alphabeta hydrolase: The nucleophile residue is Alanine located in a pentapptide GHALG (Auldridge et al.). (a similar pentapeptide GHALD with histidine as nucleophile has been found in E. Coli RutD by Knapik et al in an un related family). PIRSF037175. This family also contains esterases such as Nicotiana tabacum (Common tobacco) salicylic acid-binding protein 2. few mutations can convert one activity to the other (Padhi et al. Nedrud et al.)

Lactobacillus_peptidase

Lactococcus X-Pro dipeptidyl-peptidase proteins belong to the S15 family of the carboxypeptidase (SC) clan. These proteins, which have similar pecificity to mammalian dipeptidyl-peptidase IV, cleave Xaa-Pro-releasing N-terminal dipeptides. The penultimate residue must be proline. In Lactococcus, the proteins exist as cytoplasmic homodimers. The closest relative is Cocaine_esterase

LIDHydrolase

Family LIDHydrolase DUF2305 UPF0554 This family of proteins is conserved from plants to humans. The function is unknown. A lipid droplet hydrolase LD-associated hydrolase (LDAH) (C2orf43) with weak in vitro cholesterol hydrolase was described by Goo et al. The name DUF_2305 was replaced by LIDHydrolase

Lipase_2

Previously included in Fungal_triacylglycerol_lipase. This group of lipases has been called class 2 as they are not clearly related to other lipase families, and includes LipA and LipB from Bacillus subtilis and uncharacterised proteins from Caenorhabditis. Two other subfamilies described in: Arpigny and Jaeger (1999), Jaeger and Eggert (Family I.4 and Family I.7) are included in Lipase_2 (see classification). A novel type of hydrolase purified from Paucimonas revealed an unusual substrate specificity for amorphous poly((R)-3-hydroxyalkanoates PHA and no homologies to any other PHB depolymerase. A new family was built and extracted form Lipase_2 PHAZ7_phb_depolymerase (Arpigny_Jaeger Family IX)

Lipase_bact_N_lipase

This family has the N-terminal region of bacterial virulence factor lipase. The N-terminal region contains a potential signalling sequence. Most proteins with this N-terminal sequence have a typical alpha/beta hydrolase following in c-term. The N-terminal region is found also in proteins without lipase or alpha/beta hydrolases. The N-term domain is used to populate the family but is excluded here. Chuang et al. on aerhy-LIP found hydrolysis of p-nitrophenyl esters (optimum C10-C12) and triacylglycerols (optimum C8- C10)

lpg2422

The crystal structure of a functionally unknown protein lpg2422 from Legionella pneumophila subsp. pneumophila (4M0M) shows a N-terminal domain (1-338) with an alpha/beta hydrolase fold but the sequence homology to other families is very low. Until now this family is represented only in Legionella

Lysin_B_C_ter

Lysin B (LysB), a novel mycolylarabinogalactan esterase from mycobacteriophage, that cleaves the mycolylarabinogalactan bond to release free mycolic acids. The D29 LysB structure shows an alpha/beta hydrolase organization with a catalytic triad common to cutinases, but which contains an additional four-helix domain implicated in the binding of lipid substrates. This superfamily entry represents the linker domain of the mycobacteriophage Lysin B. The linker domain is composed of four alpha-helices connecting the C-terminal alpha-helix back to the side of the central beta-sheet.Family close to cutinases

LYsophospholipase_carboxylesterase

PLP_Cesterase. Abhydrolase_2; This family consists of both phospholipases and carboxylesterases with broad substrate specificity, but different of the family Monoglyceridelipase_lysophospholipase which is part of PF00561 AlphaBeta hydrolase. For bacterial enzymes, this family correspond to family VI of the classification of Arpigny and Jaeger (1999) The acyl protein thioesterases (APT1:LYPLA1, APT2: LYPLA2) are G protein depalmitoylases and accept also a number of S-palmitoylated protein and phospholipid substrates. Another closely related family of hydrolases: the ABHD17-depalmitoylase family contributes to the depalmitoylation of Ras-family GTPases and synaptic proteins. Burger et al. show that Acyl-protein thioesterase structures present a long tunnel for accommodation of long-chain fatty acids and release the product by use of a flexible loop tunnel lid. Homologous deacetylases use a hydrophobic residue to fix the lid and another residue to close the tunnel entrance. This causes loop rigidity changing the catalytic preference to deacetylation. SOBER1 is a protein deacetylase and not an acylprotein thioesterase. Family TE21 in ThYme database

Maspardin-ACP33-SPG21_like

ACP33 binds the intracellular domain of CD4. Mutation S109A abolishes the interraction. S109 is in similar position as active site serine of a/b hydrolase. Maspardin-ACP33-SPG21 gene is mutated in Mast Syndrome (Cross and McKusick 1967, Simpson et al 2003), a Complicated Form of hereditary spastic paraplegia associated with dementia. Ishiura et al. (2014) reported 2 Japanese brothers with autosomal recessive SPG21. The patients had onset of gait disturbances in their fifties and sixties, much later than that reported by Cross and McKusick (1967). Maspardin is conserved in metazoans but independent losses of this gene occured in two relatively distant ecdysozoan taxa: dipterans and nematodes (Chertemps etal.). Extracellular vesicles from Echinococcus granulosus (Platyhelminthe-Cestode) larval stage contain an orthologue of maspardin (Nicolao 2019). A Novel alpha/beta-hydrolase gene IbMa, homologous to maspardin, enhances salt tolerance in transgenic Sweetpotato (Liu et al. 2014)

Mbeg1-like

This bacterial family of proteins has no known function. Should be in L Block PS00120. Few Plant proteins (Selaginella moellendorffii) and Plastid group (Trypanosoma) Phospholipase A1 activity was identified as the gene product of plaA of Serratia liquefaciens Serratia sp MK1 (Givskov Molin 1993 Song et al. 1999) Phospholipase A of Yersinia enterocolitica contributes to pathogenesis in a mouse model (Schmiel et al. 1998) Gemella sanguinis 9bacl-a0a2n6sev5 protein identified as Mbeg1 in a functional multigenomic screening of human-associated bacteria for NF-kappaB-inducing bioactive effectors (Estrela et al.) since then family called Mbeg1-like (previously DUF_2974)

MenH_SHCHC

In the menaquinone biosynthesis pathway, 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase: MenH SHCHC catalyzes the formation of SHCHC, or (1 R,6 R)-2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate, by elmination of pyruvate from 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate (SEPHCHC). Is also able to catalyze the hydrolysis of the thioester bond in palmitoyl-CoA in vitro

MEST-like

Mesoderm-specific transcript (Mest) predominantly expressed in mesoderm and its derivatives is also an imprinted gene whose expression is dependent on parental origin and is designated Peg1 (paternally expressed gene-1). Curiously orthologues seem present in vertebrates, few invertebrates (molluscs, ticks, amphioxus) but not in insects or nematodes. Absent in plants and present in a limited number of bacteria

Mg-chelatase_BchO

(from InterPro) Putative magnesium chelatase accessory protein (IPR017497) : Members of this entry belong to the alpha/beta fold family of hydrolases. Members are found in bacterial genomes, if and only if, they encode anoxygenic photosynthetic systems similar to that found in Rhodobacter capsulatus (Rhodopseudomonas capsulata) and other alpha-Proteobacteria. Also proteins in this entry are often encoded in the same operon as subunits of the protoporphyrin IX magnesium chelatase, and were once designated BchO. No literature supports a role as an actual subunit of magnesium chelatase, but an accessory role is possible, as suggested by its genomic context and by its probable hydrolase activity. Hajighasemi et al. presented biochemical and structural insights into enzymatic depolymerization of polylactic acid and other polyesters.

Monoglyceridelipase_lysophospholip

This family consists of Monoglyceridelipase_lysophospholipase but different of phospholipases and carboxylesterases with broad substrate specificity. Converts monoacylglycerides to free fatty acids and glycerol. Hydrolyzes the endocannabinoid 2-arachidonoylglycerol, and thereby contributes to the regulation of endocannabinoid signaling, nociperception and perception of pain. Regulates the levels of fatty acids that serve as signaling molecules and promote cancer cell migration, invasion and tumor growth.The closest family is CarbLipBact

MpaH

Penicillium brevicompactum MpaH Hydrolase; part of the gene cluster that mediates the biosynthesis of mycophenolic acid (MPA), the first isolated antibiotic natural product in the world. Farnesyl-5,7-dihydroxy-4,6-dimethylphthalide(DHDMP) substrate of mpaH for transformation into demethylmycophenolic acid (DMMPA). The family is extracted from 6_AlphaBeta_hydrolase.

Ndr_family

RTP/Drg1/Ndr1 genes are repressed by the proto-oncogenes N-myc and c-myc. Members of this family are found in wide variety of multicellular eukaryotes, including plants (ndr nothing to do with nodal-related genes) Ndr1 included in alpha/beta hydolase PF00561 now have a Pfam family PF03096. Shaw et al Proteins 2002 May 1;47(2):163-8 identified this family as alpha/beta hydrolase. Kalaydjieva et al. showed that human-NDRG1 is mutated in hereditary motor and sensory neuropathy-Lom . Bhaduri et al. showed that ratno-ndr4 (Bdm1) is associated with hot water epilepsy. Mitchelmore et al. showed that NDRG2 is upregulated in Alzheimer's disease. NDRG1 facilitates lytic replication of Kaposi's sarcoma-associated herpesvirus by maintaining the stability of the KSHV helicase as published by Dong et al.

NFM-deformylase

Conversion of N-formylmaleamic acid to formic and maleamic acid is catalyzed by the NicD proteine from gene cluster (nic genes)), the only deformylase described so far whose catalytic triad is similar to that of some members of the alpha/beta-hydrolase fold superfamily. Nfo close relative. Family of bacterial enzymes

NLS3-Tex30

This entry consists of the KAT8 regulatory NSL complex subunit 3 (KANSL3 or NSL3, also known as testis development protein PRTD) and the testis-expressed sequence 30 proteins (TEX30). KAT8 regulatory NSL complex subunit 3 is part of the NSL complex that is involved in acetylation of nucleosomal histone H4 on several lysine residues and therefore may be involved in the regulation of transcription. Meunier et al identified KANSL3 as a microtubule minus-end-binding protein. In C. Elegans SUMV-2 interacts with SUMV-1, and they may function together with MYS-2 in a nematode KAT8/MOF-like complex to antagonise the activity of the synMuv (synthetic multivulva) genes. The function of the testis-expressed sequence 30 protein is not known.

OHBut_olig_hydro_put

Intracellular D-(-)-3-hydroxybutyrate oligomer hydrolase (also known as 3HB-oligomer hydrolase 3HBOH) functions in the degradation of poly-3-hydroxybutyrate (PHB). It catalyses the hydrolysis of D(-)-3-hydroxybutyrate oligomers (3HB-oligomers) into 3HB-monomers.

PAF-Acetylhydrolase

Platelet-activating factor acetylhydrolase (PAF-AH) is a subfamily of phospholipases A2 (group-VIIA), responsible for inactivation of platelet-activating factor through cleavage of an acetyl group (PAF: Extracellular signaling lipid; ligand for G protein-coupled platelet activating factor (PAF) receptors). Three known PAF-AHs are the brain heterotrimeric PAF-AH Ib, (whose subunits are not alpha/beta hydrolases), the extracellular, plasma PAF-AH (pPAF-AH), and the intracellular PAF-AH isoform II (PAF-AH II). Both these last two forms are alpha/beta hydrolases and are included in this family. Lipoprotein-associated phospholipase A2 (Lp-PLA2) also known as platelet-activating factor acetylhydrolase (PAF-AH) is a phospholipase A2 enzyme that in humans is encoded by the PLA2G7 gene (human-PLA2G7). This family also contains microbial lipase homologue of PAF-AH_p_II. The first sructure known was Streptomyces exfoliatus lipase

PAF_acetylhydro-like

Platelet-activating factor acetylhydrolase (PAF-AH) is a subfamily of phospholipase A2, and is involved in regulation of inflammation through the inactivation of platelet-activating factor and polar phospholipids

Palmitoyl-protein_thioesterase

Palmitoyl protein thioesterases are enzymes (EC 3.1.2.22) that remove thioester-linked fatty acyl groups such as palmitate from modified cysteine residues in proteins or peptides during lysosomal degradation. PPT1 is responsible for the removal of a palmitate group from its substrate proteins, which may include presynaptic proteins like SNAP-25, cysteine string protein (CSP), dynamin, and synaptotagmin. PPT2 removes thioester-linked fatty acyl groups from various substrates including S-palmitoyl-CoA. PPT1 and -2 perform non-redundant roles in lysosomal thioester catabolism. Neuronal ceroid lipofuscinoses (NCL) represent a group of encephalopathies that occur in 1 in 12,500 children. Mutations in the palmitoyl protein thioesterase gene (human-PPT1) causing infantile neuronal ceroid lipofuscinosis. The most common mutation results in intracellular accumulation of the polypeptide and undetectable enzyme activity in the brain. Insensitive to commonly used serine-modifying reagents phenylmethylsulfonyl fluoride (PMSF) and diisopropylfluorophosphate. See paper of structure of bovine enzyme 1EXW (Das et al. 2000). PPT2 deficiency in a recent transgenic mouse model is associated with a form of neuronal ceroid lipofuscinosis, suggesting that PPT1 and -2 perform non-redundant roles in lysosomal thioester catabolism. Peptide based reversible inhibitors may have a role as chaperone that could facilitate the transport of mutant PPT1 variants to the lysosome where improved enzyme stability may be observed in the lower pH environment Family TE20 in ThYme database

PE-PPE

This domain is found C-terminal to the PE (IPR000084) and PPE (IPR000030) domains. The secondary structure of this domain is predicted to be a mixture of alpha helices and beta strands, and recently demonstrated to be alpha/beta hydrolase: see Sultana et al. This protein domain is close to cutinase. The membrane-associated acyltransferase Chp1 (myctu-Rv3822) accepts a synthetic diacyl sulfolipid and transfers an acyl group regioselectively from one donor substrate molecule to a second acceptor molecule in two successive reactions to yield a tetraacylated product.The rv1184c locus encodes Chp2, an acyltransferase in polyacyltrehalose lipid biosynthesis In fact this domain is found in many unrelated folds only a few are alpha/beta hydrolases (Sultana 2016)

Pectinacetylesterase-Notum

Pectinacetylesterase, Pectin acetylesterases from plant pathogens act as secreted enzymes to deacetylate pectins in plant cell walls. Pectins are composed mainly of galacturonic acid residues, some of which are methylated or acetylated. Pectin acetylesterases hydrolyze the ester bond linking acetyl groups to galacturonic acid. In animals Notum acts to modify heparan sulfate proteoglycans and thereby alters the extracellular gradient of Wg/Wnt protein. Kinetic and mass spectrometric analyses of human proteins show that Notum is a carboxylesterase that removes an essential palmitoleate moiety from Wnt proteins and thus constitutes the first known extracellular protein deacylase (Kakugawa et al.). Notum also deacylates octanoylated Ghrelin. Inhibitors of NOTUM showed that NOTUM could be a potential drug target for stimulating bone formation and treating osteoporosis. Loss of Apc in intestinal stem cells drives the formation of adenomas via increased WNT signalling. Apc-mutant cells are enriched for WNT antagonist Notum. Inhibition of NOTUM limited the ability of Apc-mutant cells to expand and form intestinal adenomas

Pectin_methylesterase

Pectin methylesterase. The representative structure is BT1017 Q8A900 a methylesterases (6-O-methyl esterase)essential for pectin rhamnogalacturonan II metabolism from the gut bacterium Bacteroides thetaiotaomicron. This family is exclusivly bacterial . Plant pectin methylesterase are not alpha/bet hydrolases. In many members C-term is DUF3826 a putative sugar-binding domain. Some members are close to Acetyl-esterase_deacetylase or Abhydrolase_7. Carbohydrate Esterase Family 19 of CAZY

Peptidase_S9

Previously called Prolyl_oligopeptidase_S9 (but are not only prolyl peptidase) Peptidase_S9 are serine protease of the clan S family S9 in MEROPS database. It contains: - prolyl oligopeptidase (EC 3.4.21.26) (also called post-proline cleaving enzyme);- Escherichia coli protease II (EC 3.4.21.83) (oligopeptidase B) (gene prtB);- dipeptidyl petidase IV related proteins(EC 3.4.14.5) (DPP IV) important for the activation or inactivation of extracellular endocrine paracrine and autocrine peptides. DPPIV is synonymous with CD26 (important in HIV infection). Some members lack active serine and are probably not enzymes. The prototype structure has a beta propeller which guide substrates to the active site;- Yeast vacuolar dipeptidyl aminopeptidase A;- Acylamino-acid-releasing enzyme (EC 3.4.19.1) (acyl-peptide hydrolase).

Peptidase_S15

This entry represents a domain found peptidases Xaa-Pro dipeptidyl-peptidase and glutaryl-7-aminocephalosporanic-acid acylase, which belong to MEROPS peptidase families S15. It is also found in hydrolases from the CocE/NonD family. Cocaine esterase (CocE) hydrolyzes cocaine endowing the bacteria with the ability to utilise cocaine as a sole source of carbon and energy. YcjY-like are bacterial cell division gene

Peptidase_S37

This group of serine peptidases belong to MEROPS peptidase family S37 (clan SC). The members of this group of secreted peptidases are restricted to bacteria. In Streptomyces lividans the peptidase removes tripeptides from the N terminus of extracellular proteins (tripeptidyl aminopeptidase,Tap). The peptidase from Streptomyces mobaraensis has been shown to activate the transglutaminase precursor by removal of a leading tri- or tetrapeptide (Umezawa et al., 2004). Calcium ions enhance activity (Zotzel et al., 2003).

PGAP1

Post-GPI (Glycophosphatidylinositol; Glycosylphosphatidylinositol) attachment to proteins factor 1. The sequences found in this family are similar to PGAP1 (Q765A7_RAT). This is an endoplasmic reticulum membrane protein with a catalytic serine containing motif that is conserved in a number of lipases. PGAP1 functions as a GPI inositol-deacylase; this deacylation is important for the efficient transport of GPI-anchored proteins from the endoplasmic reticulum to the Golgi body. This family consists of several hypothetical bacterial proteins of unknown function. Members of this family have an alpha/beta hydrolase fold. The type VI lipase effectors Tle1-Tle5 secreted by the bacterial type VI secretion system (T6SS) have recently been identified as antibacterial effectors that hydrolyze membrane phospholipids. The Tle1-4 display phospholipase A1 and A2 (PLA1) (PLA2) activities. Tle1 belongs to Duf_2235 family, TLE2 to Lipase_3, TLE3 to alpha/ beta hydrolase and here Tle4 belongs to PGAP1. There are two human genes in this family. One is SERAC1. Mutations of SERAC1 causes MEGDEL syndrome, a recessive disorder of dystonia and deafness with encephalopathy and Leigh-like syndrome, impaired oxidative phosphorylation and 3-methylglutaconic aciduria. Clinical features included psychomotor retardation, recurrent infections in infancy, hypoglycemia, spasticity, dystonia, sensorineural deafness, brain atrophy, and lesions on brain imaging. Laboratory studies showed increased serum lactate and alanine, urinary 3-MGA, mitochondrial oxidative phosphorylation defects, abnormal mitochondria, an abnormal phosphatidylglycerol and cardiolipin spectrum in fibroblasts, and abnormal accumulation of unesterified cholesterol within cells.The other is PGAP1 Mutations in PGAP1 causes Mental retardation, autosomal recessive 42 MRT42

PhaC_cen_dom

(The family Pha_synthase was split in four families (PHA_synth_I, PHA_synth_II, PHA_synth_III, PhaC_cen_dom ) according to Interpro and Tigrpfam. PhaC_cen_dom groups enzyme with the central domain but not the class I,II,III domains)This entry represents the central domain of the bacterial poly-beta-hydroxybutyrate polymerase (PhaC). Polyhydroxyalkanoic acids (PHAs) are carbon and energy reserve polymers produced in some bacteria when carbon sources are plentiful and another nutrient, such as nitrogen, phosphate, oxygen, or sulphur, becomes limiting. PHAs composed of monomeric units ranging from 3 to 14 carbons exist in nature. When the carbon source is exhausted, PHA is utilised by the bacterium. PhaC links D-(-)-3-hydroxybutyrl-CoA to an existing PHA molecule by the formation of an ester bond. Poly-beta-hydroxybutyrate polymerase (PhaC) N-terminus. This entry represents the central domain of the bacterial poly-beta-hydroxybutyrate polymerase (PhaC). Polyhydroxyalkanoic acids (PHAs) are carbon and energy reserve polymers produced in some bacteria when carbon sources are plentiful and another nutrient, such as nitrogen, phosphate, oxygen, or sulphur, becomes limiting. PHAs composed of monomeric units ranging from 3 to 14 carbons exist in nature. When the carbon source is exhausted, PHA is utilised by the bacterium. PhaC links D-(-)-3-hydroxybutyrl-CoA to an existing PHA molecule by the formation of an ester bond PHA_synth_I TIGR01838 PHA_synth_II TIGR01839. The nucleophilic residue of the catalytic triad is a cysteine (with exceptions)

PHAZ7_phb_depolymerase

Thermoalkalophilic hydrolase of Paucimonas and Shewanella species with high specificity for amorphous polyesters of short chain-length hydroxyalkanoic acids. An unusual substrate specificity for amorphous poly((R)-3-hydroxyalkanoates PHA and no homologies to any other PHB depolymerase . Formerly included in Lipase_2. Family IX was introduced by Handrick et al. (Arpigny_Jaeger Family IX). Paper: Arpigny and Jaeger (1999).

PHA_depolymerase_arom

This family consists of the polyhydroxyalkanoic acid (PHA) depolymerase of Pseudomonas oleovorans and related species. This enzyme is part of polyester storage and mobilisation system as in many bacteria. However, species containing this enzyme are unusual in their capacity to produce aromatic polyesters when grown on carbon sources such as benzoic acid or phenylacetic acid

PHA_synth_I

(The family Pha_synthase was split in four families (PHA_synth_I, PHA_synth_II, PHA_synth_III, PhaC_cen_dom ) according to Interpro and Tigrpfam. PhaC_cen_dom groups enzyme with the central domain but not the class I,II,III domains)This entry represents the class I subfamily of poly(R)-hydroxyalkanoate synthases, which polymerises hydroxyacyl-CoAs with three to five carbons in the hydroxyacyl backbone into aliphatic esters termed poly(R)-hydroxyalkanoic acids. These polymers accumulate as carbon and energy storage inclusions in many species and can amount to 90 percent of the dry weight of the cell. Poly-beta-hydroxybutyrate polymerase (PhaC) N-terminus. This entry represents the central domain of the bacterial poly-beta-hydroxybutyrate polymerase (PhaC). Polyhydroxyalkanoic acids (PHAs) are carbon and energy reserve polymers produced in some bacteria when carbon sources are plentiful and another nutrient, such as nitrogen, phosphate, oxygen, or sulphur, becomes limiting. PHAs composed of monomeric units ranging from 3 to 14 carbons exist in nature. When the carbon source is exhausted, PHA is utilised by the bacterium. PhaC links D-(-)-3-hydroxybutyrl-CoA to an existing PHA molecule by the formation of an ester bond PHA_synth_I TIGR01838 PHA_synth_II TIGR01839. The nucleophilic residue of the catalytic triad is a cysteine (with exceptions)

PHA_synth_II

(The family Pha_synthase was split in four families (PHA_synth_I, PHA_synth_II, PHA_synth_III, PhaC_cen_dom ) according to Interpro and Tigrpfam PhaC_cen_dom groups enzyme with the central domain but not the class I,II,III domains). This entry represents the class II subfamily of poly(R)-hydroxyalkanoate synthases, which polymerises hydroxyacyl-CoAs, typically with six to fourteen carbons in the hydroxyacyl backbone into aliphatic esters termed poly(R)-hydroxyalkanoic acids. These polymers accumulate as carbon and energy storage inclusions in many species and can amount to 90 percent of the dry weight of cell. Poly-beta-hydroxybutyrate polymerase (PhaC) N-terminus. This entry represents the central domain of the bacterial poly-beta-hydroxybutyrate polymerase (PhaC). Polyhydroxyalkanoic acids (PHAs) are carbon and energy reserve polymers produced in some bacteria when carbon sources are plentiful and another nutrient, such as nitrogen, phosphate, oxygen, or sulphur, becomes limiting. PHAs composed of monomeric units ranging from 3 to 14 carbons exist in nature. When the carbon source is exhausted, PHA is utilised by the bacterium. PhaC links D-(-)-3-hydroxybutyrl-CoA to an existing PHA molecule by the formation of an ester bond. PHA_synth_I TIGR01838 PHA_synth_II TIGR01839. The nucleophilic residue of the catalytic triad is a cysteine (with exceptions)

PHA_synth_III_C

(The family Pha_synthase was split in four families (PHA_synth_I, PHA_synth_II, PHA_synth_III, PhaC_cen_dom ) according to Interpro and Tigrpfam. PhaC_cen_dom groups enzyme with the central domain but not the class I,II,III domains)This entry represents the PhaC subunit of a heterodimeric form of polyhydroxyalkanoic acid (PHA) synthase. Excepting the PhaC of Bacillus megaterium (which needs PhaR), all members require PhaE (IPR010123) for activity and are designated class III. This enzyme builds ester polymers for carbon and energy storage that accumulate in inclusions, and both this enzyme and the depolymerase associate with the inclusions. Class III enzymes polymerise short-chain-length hydroxyalkanoates. Poly-beta-hydroxybutyrate polymerase (PhaC) N-terminus. This entry represents the central domain of the bacterial poly-beta-hydroxybutyrate polymerase (PhaC). Polyhydroxyalkanoic acids (PHAs) are carbon and energy reserve polymers produced in some bacteria when carbon sources are plentiful and another nutrient, such as nitrogen, phosphate, oxygen, or sulphur, becomes limiting. PHAs composed of monomeric units ranging from 3 to 14 carbons exist in nature. When the carbon source is exhausted, PHA is utilised by the bacterium. PhaC links D-(-)-3-hydroxybutyrl-CoA to an existing PHA molecule by the formation of an ester bond PHA_synth_I TIGR01838 PHA_synth_II TIGR01839. The nucleophilic residue of the catalytic triad is a cysteine (with exceptions)

PHB_depolymerase_PhaZ

C-terminus of bacterial poly(3-hydroxybutyrate) (PHB) de-polymerase. This enzyme degrades PHB granules to oligomers and monomers of 3-hydroxy-butyric acid. Intracellular depolymerase for polyhydroxyalkanoate (PHA), a carbon and energy storing polyester that accumulates in granules in many bacterial species when carbon sources are abundant but other nutrients are limiting.

Pheophytinase

Pheophytin pheophorbide hydrolase (pheophytinase) is involved in chlorophyll breakdown during leaf senescence. Chlorophyllase (the other first step chrorophylle degrading enzyme) is not localized to plastids, and double knockout mutant plants still are able to degrade chlorophyll during leaf senescence. So pheophytinase is a new pathway. This entry represents a group of pheophytinases from plants, including PPH, a chloroplast-located and senescence-induced hydrolase widely distributed in algae and land plants. In Arabidopsis, PPH (also known as CRN1) specifically dephytylates the Mg-free chlorophyll pigment, pheophytin (phein), yielding pheophorbide .It plays a crucial role in Chlorophyll degradation during leaf senescence

PhoPQ_related

IPR009199 PIRSF014728 PhoPQ-activated pathogenicity-related protein, PqaA type. Proteins in this entry are believed to play a role in virulence/pathogenicity in Salmonella. Salmonella typhi PqaA has been shown to be activated by PhoP/Q two-component regulatory system, which regulates many virulence genes Baker et al 1997. It has been also shown to confer resistance to antimicrobial peptides (melittin). Autocrine proliferation repressor protein A (AprA, CfaD) is a protein secreted by Dictyostelium discoideum cells. AprA has DPPIV-like protease activity

PlaB

Bacterial phospholipases. Legionella pneumophila possesses a major cell-associated hemolytic phospholipase A (PlaB) which shares no homology to described phospholipases. PlaB preferentially hydrolyzes long-chain fatty acid substrates containing 12 or more carbon atoms. PlaB shows concentration-dependent phospholipase inactivation by tetramerization which may be a mechanism for self-protection. See Papers Bender et al. 2009 and Kuhle et al. 2014 The tetramer is a dimer of identical dimers. Diwo et al. found in the structure eight NAD(H) molecules at the dimer/dimerinterface, suggesting that these molecules stabilize the tetramer leading to enzyme inactivation

Plasmodium_subtelomeric_PST-A

These proteins represent a paralogous family of genes found in Plasmodium falciparum and Plasmodium yoelii that are closely related to various phospholipases and lysophospholipases of plants as well as generally being related to the alpha/beta-fold superfamily of hydrolases. These genes are preferentially located in the subtelomeric regions of the chromosomes of both P. falciparum and P. yoelii. TIGRFAMs TIGR01607 (PST-A). Close sequences of other Apicomplexa species were included

PMH_Peptidase_S9

Puromycine hydrolase (and also pQQM from Pseudomonas, C. Elegans dp4). Some Streptomyces strains produce Puromycin (PM classified into a family of nucleoside antibiotics) and express a PM-inactivating enzyme as a self-resistance determinant which is homologous to Peptidase S9

PolyAspartate-hydrolase

Poly(aspartate) (PAA) is a bio-based, biocompatible, biodegradable alternative to polycarboxylate of poly(acrylate). Bacterial PAA-hydrolyzing enzyme can also perform synthesis of poly(alpha-ethyl beta-aspartate). This family is close to PHB depolymerase. The LpqC, poly(3-hydroxybutyrate) depolymerase from Bordetella parapertussis (CASP Target) (structure 3D0K) belongs to this family. Polyaspartic acid (PASA) is also a natural polymer as fragment of larger proteins with length up to 50 amino acids. Synthetic tPAA(thermally synthesized PAA) consists of beta-amide (70%) and alpha-amide,(30%) D- and L-aspartate units; the alpha- and beta-amide units are randomly distributed. PAA hydrolase-1 is an alpha beta hydrolase inhibited by PMSF and DFP. PAA hydrolase-2 is closer to metallo carboxypeptidase inhibited by DFP and PMSF

PPase_methylesterase_euk

PIRSF022950 This group represents protein phosphatase methylesterase, eukaryotic type. Carboxymethylation of proteins is a highly conserved means of regulation in eukaryotic cells. The protein phosphatase 2A (PP2A) catalytic (C) subunit is reversibly methylated at its carboxyl terminus by specific methyltransferase and methylesterase enzymes. Protein phosphatase 2A (PP2A) is an important serine/threonine phosphatase that plays a role in many biological processes. Reversible carboxyl methylation of the PP2A catalytic subunit is an essential regulatory mechanism for its function. Demethylation and negative regulation of PP2A is mediated by a PP2A-specific methylesterase PME-1, which is conserved from yeast to humans. PME-1 directly binds to the active site of PP2A. This interaction results in the activation of PME-1 by rearranging the catalytic triad into an active conformation. Interactions also lead to inactivation of PP2A by evicting the manganese ions required for the phosphatase activity (Xing et al. ). PPME proteins show false positive hits with the prosite PS00120 of lipases

Proline_iminopeptidase

This entry describes a subfamily of the alpha/beta fold family. This entry represents a of serine peptidase belonging to peptidase family S33 (clan SC). Family members include prolinases (Pro-Xaa dipeptidase, EC:3.4.13.18), prolyl aminopeptidases (EC:3.4.11.5), and a leucyl aminopeptidase. Prolyl aminopeptidase Pro_amnoPtase (S33 family) PROAMNOPTASE Pept_S33_TRI_F1 Pro_imino_pep_2. (Crystal structure of the proline iminopeptidase-related protein TTHA1809 from Thermus thermophilus HB8 (2YYS) showed that it lacks the active site serine and probably similar proteins play non enzymatic role in a few bacteria: Okai et al.2008)

Prolylcarboxypeptidase

S28 peptidases in MEROPS database. These serine proteases include several eukaryotic enzymes such as lysosomal Pro-X carboxypeptidase, dipeptidyl-peptidase II, and thymus-specific serine peptidase. In human the S28 family of peptidases consists of three enzymes, PRCP, TSSP and DPP7. DPP7 is also called dipeptidyl peptidase 2 and quiescent cell proline dipeptidase. TSSP is thymus-specific serine protease. PRCP is a lysosomal, serine carboxypeptidase that cleaves hydrophobic C-terminal amino acids adjacent to proline. In contrast, DPP7 is a serine dipeptidyl aminopeptidase that cleaves N-terminal amino acids adjacent to proline and is localized to intracellular vesicles

Prolyl_oligopeptidase_S9

Prolyl_oligopeptidase_S9 are serine protease of the clan S family S9 in MEROPS database. Previously this family contained also all the subfamilies ACPH_Peptidase_S9, Glutamyl_Peptidase_S9, DPP4N_Peptidase_S9, S9N_Peptidase_S9. Now it contains entries that do not fit in these well defined sub families. Few proteins characterized in this family. Aspergillus fumigatus DPP5 and DPP4.(Beauvais et al.) DPP5 unique substrate specificity limited to the hydrolysis of X-Ala, His-Ser, and Ser-Tyr dipeptide and not post Proline

RsbQ-like

The RsbQ alpha/beta hydrolase and RsbP serine phosphatase form a signaling pair required to activate the general stress factor Sigma factor sigb of Bacillus subtilis in response to energy limitation. In plants RsbQ-like proteins could function downstream of strigolactone synthesis (Strigolactones are endogenous butenolide hormones that regulate shoot and root architecture, and stimulate the branching of arbuscular mycorrhizal fungi). DWARF14(D14) act as component of hormone signaling or as enzymes that participates in the conversion of strigolactones to the bioactive form. Karrikins (KARs) represent a family of butenolide compounds found in smoke that trigger the germination of many species after fire. KAI2 (karrikin-insensitive2) is required for normal seed germination and seedling growth. Conn et al. showed that convergent evolution of strigolactone perception enabled host detection in parasitic plants. Mutations in KAI2, encoding the proposed karrikin receptor, result in hypersensitivity to water deprivation.. The parasite Striga hermonthica is causing severe yield losses of cereals in sub-Saharan Africa. The germination of Striga seeds relies on host-released strigolactones (SLs) signaling molecules. SL analogs are developped as 'suicidal germination agents'(The induction of Striga seeds germination in the absence of the host leads to the death of germinating parasite). Wang et al. show that origins of strigolactone and karrikin signaling in plants could come from horizontal transfer from bacteria. The fungi D14 Fungal-D14-Strigolactone-R although homologous to family RsbQ-like of plant strigolactone receptors are somewhat far related and cannot supplement lack of receptor in arabidopsis for example

RutD

RutD is encoded within the Rut operon which allows growth on pyrimidines as sole nitrogen source. The function of this protein is not known, but it is necessary for growth on pyrimidines, and cells lacking RutD produce much less of the Rut pathway intermediate malonic semialdehyde than normal. It is thought that RutD increases the rate of spontaneous hydrolysis of the toxic intermediate aminoacrylate to malonic semialdehyde. The closest relative family is Carboxymethylbutenolide_lactonase. The structure of E. Coli RutD by Knapik et al. revealed a new active site for an alphabeta hydrolase: The nucleophile residue is Histidine located in a pentapptide GHALG. (a similar pentapeptide GHALD with alanine as nucleophile has been found in an un related family Methylketone synthase 1 in hydroxylnitrile lyase Auldridge et al.)

S9N_PPCE_Peptidase_S9

prolyl oligopeptidase (EC 3.4.21.26) (also called post-proline cleaving enzyme PPCE, Prolyl endopeptidase PE, prolyl oligopeptidase POP). Prolyl oligopeptidases are either located in the cytosol or they are membrane bound, where they cleave peptide bonds with prolyl P1 specificities (but cleavage of alanyl bonds has been detected). The proline must adopt a trans con- figuration within the chain. Peptides of up to 30 residues are cleaved. N-terminal domain is a 7-bladed beta-propeller

S9N_PREPL_Peptidase_S9

a prolyl endopeptidase-like enzyme by name only; a (thio)esterase involved in mitochondrial respiratory chain function (Rosier et al.). PREPL Prolylendopeptidase-like. Prolyl oligopeptidase (EC 3.4.21.26) (also called post-proline cleaving enzyme). N-terminal domain is a 7-bladed beta-propeller. In contrast to PREP and oligopeptidase B, which require both amino- and carboxy-terminal sequences for activity, PREPL activity appeared to depend only on the carboxy-terminal domain. Deletion of PREPL was found in patients with hypotonia-cystinuria syndrome Parvari et al. (2001, 2005) Jaeken et al. (2006)

SERHL

SERHL SHL SEHL kraken-like. Serine hydrolase-like protein. This gene may have been partially duplicated (AC Q9NQF3) may be a pseudogene. In mouse, induced by passive stretch of skeletal muscle in vivo (Sadusky et al ). Testis secretory sperm-binding protein Li 216e. KRAKEN in drosophila. May have a role in detoxification and digestion during embryogenesis and larval development. Ubiquitously expressed before embryonic stage 11. By stage 15, in gastric caeca, pharynx, posterior spiracles and anterior edge of midgut. At the end of embryogenesis, expression is confined to gastric caeca. During third instar larvae, expressed at low levels in gastric caeca, midgut and hindgut and high level in fat body.

Tannase

Tannase and feruloyl esterase. This family includes fungal tannase and feruloyl esterase type C (FAE-C).Tannases hydrolyze the galloyl ester bond in tannins to release gallic acid. It also includes several bacterial homologues of unknown function. aspor-q2uh24 is neither a feruloyl esterase nor a tannase but a paraben hydrolase (Koseki et al.). MHETase from Ideonella sakaiensis idesa-mheth does not show activity on pNP-aliphatic esters or typical aromatic ester compounds catalyzed by the tannase family enzymes, such as ethyl gallate and ethyl ferulate. However some mutants of idesa-mheth can hydrolyze BHET ( Palm et al.). It is an exo-PETase. Another family of bacterial tannases has been described: Tannase_Bact. Two enzymes in Ideonella sakaiensis (for example) act on PET (Poly ethylene terephthalate): idesa-peth from Polyesterase-lipase-cutinase family and idesa-mheth which acts on extremity of PET (Exo-PETase Function) and on MHET the product of hydrolysis of PET. MHETase belongs to the Tannase family

Thioesterase

Thioesterase domains often occur integrated in or associated with peptide synthetases which are involved in the non-ribosomal synthesis of peptide antibiotics. Thioesterases are required for the addition of the last amino acid to the peptide antibiotic, thereby forming a cyclic antibiotic. Only the last domain TE thioesterase of the acv synthetase (acvs) is included in ESTHER (Polyketide synthase Polyene PKS). Human fatty acid synthase (FAS) is uniquely expressed at high levels in many tumor types. Pharmacological inhibition of FAS therefore represents an important therapeutic opportunity. The drug Orlistat, which has been approved by the US Food and Drug Administration, inhibits FAS, induces tumor cell-specific apoptosis. Families TE-16 TE-17 TE-18 in ThYme database

Thioesterase_acyl-transferase

This bacterial family of Acyl transferases (ACT or myristoyl-acp-specific thioesterases) catalyses the first step in the bioluminescent fatty acid reductase system, which is required for aldehyde biosynthesis. This enzyme belongs to the LuxD family. Together with acyl-protein synthetase (LuxE) and reductase (LuxC), it belongs to a multienzyme complex. This complex channels activated fatty acids into the aldehyde substrate for the luciferase-catalyzed bacterial bioluminescence reaction. The C-terminal region of LuxD interacts with LuxE to causes a conformational change. LuxD has a calculated M(r) of 34,384 and comprises 305 aa residues. Induction of luminescence only occurs at high cell density. Some bacteria have N-acylhomoserine lactone autoinducers for luminescence. Warning: the serine 77 in GXSXG motif is not the active site serine 114 as determined by X ray structure AASLS in Vibrio harveyi see Lawson_1994_Biochemistry_33_9382. Family TE19 in ThYme database

Thiohydrolase

Under construction: extracted from Xaa-Pro-like_dom. Penicillium sp. Chain-fusing Polyketide Gregatin A GrgF belongs to this family.Thioesterase DcsB: A Polyketide Cyclase That Forms Medium-Ring Lactones. The nucleophile can be Ser as in beab2-j4wat9 (Beauveria bassiana (White muscardine disease fungus) thioesterase DcsB) or Cys as in pensq-GrgF (Penicillium sp. Chain-fusing Polyketide Gregatin A GrgF). The C115S mutant functions as a thioesterase, while losing the ability to perform chain fusion

TTHA1544-like

Minimal hydrolase fold from Thermus thermophilus (one strand less than the cutinase-like family); there is neither catalytic triad, nor nucleopilic residue in the elbow motif. The adjacent gene TTHA1545 is complementary (C-term) to this sequence but not in the same frame and not in the right order

UCP031088

Family of plant proteins: IPR016969 Uncharacterised conserved protein UCP031088, alpha/beta hydrolase, At1g15070

UCP031982

The eucaryote members are probably contaminant PIRSF031982 UCP031982_abhydr This group represents a predicted alpha/beta hydrolase, XabL type. For bacterial enzymes, this family correspond to family V.3 of the classification of Arpigny and Jaeger 1999. This is a family of bacterial enzymes.

UCP033634

Family of Bacterial proteins mostly Terrabacteria group and mostly Bacillus species

UCP037442

PIRSF037442 UCP037442_abhydr This group represents a predicted alpha/beta hydrolase, RSp0795 type.

UPF0255

DUF1100 UPF0255. The family was split in two. Duf_1100-S with active site (S217 in (GXSXG) D300 H329) as in artni-Q93NG6, and Duf_1100-R (R53, D203, R 272 (in GXRXG)) as in FrsA. This family is represented by a C-C bond cleaving alpha/beta-hydrolase involved in nicotine degradation: 2,6-dihydroxy-pseudo-oxynicotine hydrolase from the nicotine-degradation pathway of Arthrobacter nicotinovorans (artni-Q93NG6a) (Schleberger et al.). The fermentation/respiration switch protein FrsA (product of the yafA gene in E. Coli (ecoli-yafa)(vibvy-y856) binds the dephosphorylated form of glucose-specific enzyme IIAGl the interaction increases the glucose fermentation under oxygen-limited conditions. FrsA is a pyruvate decarboxylase (Lee et al.)(In Scop 2,6-dihydropseudooxynicotine hydrolase) Thus there are two functions and two different active sites in this family (nucleophile elbow: GXSXG in hydrolase, GXRXG in decarboxylase). However (Kellett et al.) showed Computational, structural, and kinetic evidence that Vibrio vulnificus FrsA is not a cofactor-independent pyruvate decarboxylase. The family also includes the hydrolytic polyketide shortening protein Ayg1 from fungi (Fujii et al.), and Fus2 from Gibberella species, which is part of the gene cluster that mediates the biosynthesis of the mycotoxin fusarin C. Fus2 catalyses closure of the 2-pyrrolidone ring of the intermediate 20-hydroxy-prefusarin to form another intermediate, 20-hydroxy-fusarin, which is then oxidized by Fus8 (Niehaus et al.). Other members of this family are still uncharacterised

Valacyclovir-hydrolase

Biphenyl hydrolase-like; BPHL, Valacyclovirase, Mucin-associated antigen, MCNAA, Breast epithelial Mucin-associated antigen. Alpha-amino acid ester hydrolase that prefers small, hydrophobic, and aromatic side chains and does not have a stringent requirement for the leaving group other than preferring a primary alcohol. Valacyclovir (VACV) is the 5-prime valyl ester prodrug of acyclovir, an effective antiherpetic drug. VACV is relatively stable in gut lumen while very susceptible to intracellular enzymatic hydrolysis.

VirJ

Bacterial virulence protein (VirJ). This family contains several bacterial VirJ virulence proteins. VirJ is in the vir region of an octopine-type Ti plasmid. VirJ is similarto of a chromosomal gene acvB, which is required for tumorigenesis. Any one of these genes are required for T-DNA transfer into plants. VirJ is thought to be involved in the type IV secretion system. It is thought that the substrate proteins localised to the periplasm may associate with the pilus in a manner that is mediated by VirJ, and suggest a two-step process for type IV secretion in Agrobacterium

Xaa-Pro-like_dom

Under construction: AidA is a new quorum quenching enzyme. Inhibits motility and biofilm formation. Could contribute in bacterial competition, as it is capable of hydrolyzing the signaling molecules that mediate interspecies communication.

YcjY-like

Bacterial proteins. Enzymes of unknown function. YcjY gene involved in uptake and degradation of murein tripeptide under nitrogen starvation in E.Coli. Bacterial cell division gene

Zearalenone-hydrolase

The mycotoxin zearalenone has been contaminating maize and other grains. Zearalenone is a macrolide comprising a fourteen-membered lactone fused to 1,3-dihydroxybenzene, a member of resorcinols; a potent estrogenic metabolite produced by some Giberella species. It has a role as a fungal metabolite and a mycoestrogen. It can be hydrolyzed and inactivated by the lactonase ZHD. Zearalenone differs from other quorum-sensing lactones


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Please cite: Lenfant 2013 Nucleic.Acids.Res. or Marchot Chatonnet 2012 Prot.Pept Lett.
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