Hydroxynitrile_lyase

Relationship

Family: Hydroxynitrile_lyase

Block: X

Parent Family: Abhydrolase_6

Comment

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 (AtMES1 - AtMES20). 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 pentapeptide 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.). Some millipedes are able to exude toxic hydrogen cyanide as a defense, but hydroxynitril lyase from millipedes are not alpha/beta hydrolases

Database

Sequences

Peptide in Fasta
Nucleotide in Fasta
Alignment with Multalin Text only
Seed alignment with MAFFT No colour
Alignment with MAFFT No colour
Dendrogram The dnd file

Structures (57)

Genes Proteins in Hydroxynitrile_lyase family (219)

Fragments of genes in Hydroxynitrile_lyase family (30)

Structures in Hydroxynitrile_lyase family (57)

Substrates in Hydroxynitrile_lyase family (17)

Inhibitors in Hydroxynitrile_lyase family (14)

References (11)

Title : Evolution of a Catalytic Mechanism - Rauwerdink_2016_Mol.Biol.Evol_33_971
Author(s) : Rauwerdink A , Lunzer M , Devamani T , Jones B , Mooney J , Zhang ZJ , Xu JH , Kazlauskas RJ , Dean AM
Ref : Molecular Biology Evolution , 33 :971 , 2016
PubMedID: 26681154
Gene_locus related to this paper: 9zzzz-5TDX , hevbr-hnl

Title : Uncovering divergent evolution of alpha\/beta-hydrolases: a surprising residue substitution needed to convert hydroxynitrile lyase into an esterase - Nedrud_2014_Chem.Sci_5_4265
Author(s) : Nedrud DM , Lin H , Lopez G , Padhi SK , Legatt GA , Kazlauskas RJ
Ref : Chem Sci , 5 :4265 , 2014
PubMedID: 25346843
Gene_locus related to this paper: hevbr-hnl , nicta-SABP2

Title : Hydroxynitrile lyases with alpha\/beta-hydrolase fold: two enzymes with almost identical 3D structures but opposite enantioselectivities and different reaction mechanisms - Andexer_2012_Chembiochem_13_1932
Author(s) : Andexer JN , Staunig N , Eggert T , Kratky C , Pohl M , Gruber K
Ref : Chembiochem , 13 :1932 , 2012
PubMedID: 22851196
Gene_locus related to this paper: arath-HNL

Title : Emergent decarboxylase activity and attenuation of alpha\/beta-hydrolase activity during the evolution of methylketone biosynthesis in tomato - Auldridge_2012_Plant.Cell_24_1596
Author(s) : Auldridge ME , Guo Y , Austin MB , Ramsey J , Fridman E , Pichersky E , Noel JP
Ref : Plant Cell , 24 :1596 , 2012
PubMedID: 22523203
Gene_locus related to this paper: solha-e0ycs2

Title : Switching from an esterase to a hydroxynitrile lyase mechanism requires only two amino acid substitutions - Padhi_2010_Chem.Biol_17_863
Author(s) : Padhi SK , Fujii R , Legatt GA , Fossum SL , Berchtold R , Kazlauskas RJ
Ref : Chemical Biology , 17 :863 , 2010
PubMedID: 20797615
Gene_locus related to this paper: hevbr-hnl , nicta-SABP2

Title : Uneven twins: comparison of two enantiocomplementary hydroxynitrile lyases with alpha\/beta-hydrolase fold - Guterl_2009_J.Biotechnol_141_166
Author(s) : Guterl JK , Andexer JN , Sehl T , von Langermann J , Frindi-Wosch I , Rosenkranz T , Fitter J , Gruber K , Kragl U , Eggert T , Pohl M
Ref : J Biotechnol , 141 :166 , 2009
PubMedID: 19433222
Gene_locus related to this paper: arath-HNL , hevbr-hnl , manes-hnl

Title : Inactive methyl indole-3-acetic acid ester can be hydrolyzed and activated by several esterases belonging to the AtMES esterase family of Arabidopsis - Yang_2008_Plant.Physiol_147_1034
Author(s) : Yang Y , Xu R , Ma CJ , Vlot AC , Klessig DF , Pichersky E
Ref : Plant Physiol , 147 :1034 , 2008
PubMedID: 18467465
Gene_locus related to this paper: arath-MES17 , arath-AT4G16690 , arath-AT4G37150 , arath-MES6 , arath-MES7 , arath-MES3 , arath-MES1 , arath-MES18 , arath-MES10 , arath-MES19

Title : Reaction mechanism of hydroxynitrile lyases of the alpha\/beta-hydrolase superfamily: the three-dimensional structure of the transient enzyme-substrate complex certifies the crucial role of LYS236 - Gruber_2004_J.Biol.Chem_279_20501
Author(s) : Gruber K , Gartler G , Krammer B , Schwab H , Kratky C
Ref : Journal of Biological Chemistry , 279 :20501 , 2004
PubMedID: 14998991
Gene_locus related to this paper: hevbr-hnl

Title : High-affinity salicylic acid-binding protein 2 is required for plant innate immunity and has salicylic acid-stimulated lipase activity - Kumar_2003_Proc.Natl.Acad.Sci.U.S.A_100_16101
Author(s) : Kumar D , Klessig DF
Ref : Proc Natl Acad Sci U S A , 100 :16101 , 2003
PubMedID: 14673096
Gene_locus related to this paper: nicta-SABP2

Title : Structure determinants of substrate specificity of hydroxynitrile lyase from Manihot esculenta - Lauble_2002_Protein.Sci_11_65
Author(s) : Lauble H , Miehlich B , Forster S , Kobler C , Wajant H , Effenberger F
Ref : Protein Science , 11 :65 , 2002
PubMedID: 11742123
Gene_locus related to this paper: manes-hnl

Title : Molecular cloning of the full-length cDNA of (S)-hydroxynitrile lyase from Hevea brasiliensis. Functional expression in Escherichia coli and Saccharomyces cerevisiae and identification of an active site residue - Hasslacher_1996_J.Biol.Chem_271_5884
Author(s) : Hasslacher M , Schall M , Hayn M , Griengl H , Kohlwein SD , Schwab H
Ref : Journal of Biological Chemistry , 271 :5884 , 1996
PubMedID: 8621461
Gene_locus related to this paper: hevbr-hnl