Palmitoyl-protein_thioesterase

Relationship

Family: Palmitoyl-protein_thioesterase

Block: X

Parent Family: No family

Comment

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

Database

Interpro : IPR002472 Palmitoyl protein thioesterase , IPR030295 Lysosomal thioesterase PPT2 , IPR030294 Palmitoyl-protein thioesterase 1

PIRSF : No PIRSF

Pdoc : No Pdoc

Pfam : PF02089 Palm_thioest

Prints : PR00414

EC Number : 3.1.2.22

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 (5)

Genes Proteins in Palmitoyl-protein_thioesterase family (59)

Fragments of genes in Palmitoyl-protein_thioesterase family (13)

Structures in Palmitoyl-protein_thioesterase family (5)

Substrates in Palmitoyl-protein_thioesterase family (1)

Inhibitors in Palmitoyl-protein_thioesterase family (7)

References (17)

Title : Thioesterase enzyme families: Functions, structures, and mechanisms - Caswell_2021_Protein.Sci__
Author(s) : Caswell BT , de Carvalho CC , Nguyen H , Roy M , Nguyen T , Cantu DC
Ref : Protein Science , : , 2021
PubMedID: 34921469

Title : Depalmitoylation by Palmitoyl-Protein Thioesterase 1 in Neuronal Health and Degeneration - Koster_2019_Front.Synaptic.Neurosci_11_25
Author(s) : Koster KP , Yoshii A
Ref : Front Synaptic Neurosci , 11 :25 , 2019
PubMedID: 31555119
Gene_locus related to this paper: human-PPT1

Title : Temporal Profiling Establishes a Dynamic S-Palmitoylation Cycle - Won_2018_ACS.Chem.Biol_13_1560
Author(s) : Won SJ , Martin BR
Ref : ACS Chemical Biology , 13 :1560 , 2018
PubMedID: 29733200

Title : Infantile neuronal ceroid lipofuscinosis: follow-up on a Spanish series - Perez-Poyato_2012_Gene_499_297
Author(s) : Perez Poyato MS , Mila Recansens M , Ferrer Abizanda I , Domingo Jimenez R , Lopez Lafuente A , Cusi Sanchez V , Rodriguez-Revenga L , Coll Rosell MJ , Gort L , Poo Arguelles P , Pineda Marfa M
Ref : Gene , 499 :297 , 2012
PubMedID: 22387303
Gene_locus related to this paper: human-PPT1

Title : ThYme: a database for thioester-active enzymes - Cantu_2011_Nucleic.Acids.Res_39_D342
Author(s) : Cantu DC , Chen Y , Lemons ML , Reilly PJ
Ref : Nucleic Acids Research , 39 :D342 , 2011
PubMedID: 21045059

Title : Thioesterases: a new perspective based on their primary and tertiary structures. - Cantu_2010_Protein.Sci_19_1281
Author(s) : Cantu DC , Chen Y , Reilly PJ
Ref : Protein Science , 19 :1281 , 2010
PubMedID: 20506386

Title : Palmitoyl:protein thioesterase (PPT1) inhibitors can act as pharmacological chaperones in infantile Batten disease - Dawson_2010_Biochem.Biophys.Res.Commun_395_66
Author(s) : Dawson G , Schroeder C , Dawson PE
Ref : Biochemical & Biophysical Research Communications , 395 :66 , 2010
PubMedID: 20346914
Gene_locus related to this paper: human-PPT1

Title : The crystal structure of palmitoyl protein thioesterase-2 (PPT2) reveals the basis for divergent substrate specificities of the two lysosomal thioesterases, PPT1 and PPT2 - Calero_2003_J.Biol.Chem_278_37957
Author(s) : Calero G , Gupta P , Nonato MC , Tandel S , Biehl ER , Hofmann SL , Clardy J
Ref : Journal of Biological Chemistry , 278 :37957 , 2003
PubMedID: 12855696
Gene_locus related to this paper: human-PPT2

Title : Adult neuronal ceroid lipofuscinosis with palmitoyl-protein thioesterase deficiency: first adult-onset patients of a childhood disease - van Diggelen_2001_Ann.Neurol_50_269
Author(s) : van Diggelen OP , Thobois S , Tilikete C , Zabot MT , Keulemans JL , van Bunderen PA , Taschner PE , Losekoot M , Voznyi YV
Ref : Annals of Neurology , 50 :269 , 2001
PubMedID: 11506414
Gene_locus related to this paper: human-PPT1

Title : The crystal structure of palmitoyl protein thioesterase 1 and the molecular basis of infantile neuronal ceroid lipofuscinosis - Bellizzi_2000_Proc.Natl.Acad.Sci.U.S.A_97_4573
Author(s) : Bellizzi JJ, 3rd , Widom J , Kemp C , Lu JY , Das AK , Hofmann SL , Clardy J
Ref : Proc Natl Acad Sci U S A , 97 :4573 , 2000
PubMedID: 10781062
Gene_locus related to this paper: bovin-ppt , human-PPT1

Title : Structural basis for the insensitivity of a serine enzyme (palmitoyl-protein thioesterase) to phenylmethylsulfonyl fluoride - Das_2000_J.Biol.Chem_275_23847
Author(s) : Das AK , Bellizzi JJ, 3rd , Tandel S , Biehl E , Clardy J , Hofmann SL
Ref : Journal of Biological Chemistry , 275 :23847 , 2000
PubMedID: 10801859
Gene_locus related to this paper: bovin-ppt2 , human-PPT1

Title : Mutations in the palmitoyl-protein thioesterase gene (PPT\; CLN1) causing juvenile neuronal ceroid lipofuscinosis with granular osmiophilic deposits - Mitchison_1998_Hum.Mol.Genet_7_291
Author(s) : Mitchison HM , Hofmann SL , Becerra CH , Munroe PB , Lake BD , Crow YJ , Stephenson JB , Williams RE , Hofman IL , Taschner PE , Martin JJ , Philippart M , Andermann E , Andermann F , Mole SE , Gardiner RM , O'Rawe AM
Ref : Hum Mol Genet , 7 :291 , 1998
PubMedID: 9425237
Gene_locus related to this paper: human-PPT1

Title : Molecular genetics of palmitoyl-protein thioesterase deficiency in the U.S - Das_1998_J.Clin.Invest_102_361
Author(s) : Das AK , Becerra CH , Yi W , Lu JY , Siakotos AN , Wisniewski KE , Hofmann SL
Ref : Journal of Clinical Investigation , 102 :361 , 1998
PubMedID: 9664077
Gene_locus related to this paper: human-PPT1

Title : A novel insertion mutation (A169i) in the CLN1 gene is associated with infantile neuronal ceroid lipofuscinosis in an Italian patient - Santorelli_1998_Biochem.Biophys.Res.Commun_245_519
Author(s) : Santorelli FM , Bertini E , Petruzzella V , Di Capua M , Calvieri S , Gasparini P , Zeviani M
Ref : Biochemical & Biophysical Research Communications , 245 :519 , 1998
PubMedID: 9571187
Gene_locus related to this paper: human-PPT1

Title : Didemnin binds to the protein palmitoyl thioesterase responsible for infantile neuronal ceroid lipofuscinosis - Crews_1996_Proc.Natl.Acad.Sci.U.S.A_93_4316
Author(s) : Crews CM , Lane WS , Schreiber SL
Ref : Proc Natl Acad Sci U S A , 93 :4316 , 1996
PubMedID: 8633062
Gene_locus related to this paper: human-PPT1

Title : Lipid thioesters derived from acylated proteins accumulate in infantile neuronal ceroid lipofuscinosis: correction of the defect in lymphoblasts by recombinant palmitoyl-protein thioesterase - Lu_1996_Proc.Natl.Acad.Sci.U.S.A_93_10046
Author(s) : Lu JY , Verkruyse LA , Hofmann SL
Ref : Proc Natl Acad Sci U S A , 93 :10046 , 1996
PubMedID: 8816748
Gene_locus related to this paper: human-PPT1

Title : Mutations in the palmitoyl protein thioesterase gene causing infantile neuronal ceroid lipofuscinosis - Vesa_1995_Nature_376_584
Author(s) : Vesa J , Hellsten E , Verkruyse LA , Camp LA , Rapola J , Santavuori P , Hofmann SL , Peltonen L
Ref : Nature , 376 :584 , 1995
PubMedID: 7637805
Gene_locus related to this paper: human-PPT1