EzCatDB: S00350

DB codeS00350
RLCP classification1.14.30000.10
CATH domainDomain 13.40.50.1820Catalytic domain
E.C.3.1.2.22
CSA1eh5

CATH domainRelated DB codes (homologues)
3.40.50.1820S00544,S00344,S00517,S00525,S00526,S00720,S00723,S00724,S00725,S00919,S00057,S00374,S00345,S00347,S00348,S00346,S00352,S00353,S00355,S00356,S00358,D00189,D00210,D00539,T00253

Enzyme Name
Swiss-protKEGG

P45478O75608
Protein namePalmitoyl-protein thioesterase 1Acyl-protein thioesterase 1palmitoyl[protein] hydrolase
palmitoyl-protein thioesterase
palmitoyl-(protein) hydrolase
SynonymsPPT-1
EC 3.1.2.22
Palmitoyl-protein hydrolase 1
EC 3.1.2.-
Lysophospholipase 1
Lysophospholipase I

KEGG pathways
MAP codePathways
MAP00062Fatty acid elongation in mitochondria

Swiss-prot:Accession NumberP45478O75608
Entry namePPT1_BOVINLYPA1_HUMAN
ActivityPalmitoyl-protein + H(2)O = palmitate + protein.Palmitoyl-protein + H(2)O = palmitate + protein.
Subunit
Homodimer.
Subcellular locationLysosome.Cytoplasm (By similarity).
Cofactor



SubstratesProductsintermediates
KEGG-idC06412C00001C00249C00017I00147I00085I00086
CompoundPalmitoyl-proteinH2OPalmitateProteinPeptidyl-Ser-tetrahedral intermediate (with previous thioester)Acyl-enzyme(Peptidyl-Ser-acyl group)Peptidyl-Ser-tetrahedral-intermediate
Typelipid,peptide/proteinH2Ofatty acidpeptide/protein


1eh5AUnbound
UnboundUnboundUnboundIntermediate-bound:PLMUnbound
1ei9AUnbound
UnboundUnboundUnboundUnboundUnbound
1exwAUnbound
UnboundUnboundUnboundUnboundIntermediate-analogue:HDS
1fj2AUnbound
UnboundUnboundUnboundUnboundUnbound
1fj2BUnbound
UnboundUnboundUnboundUnboundUnbound

Active-site residues
pdbCatalytic residuesMain-chain involved in catalysis
1eh5ASER 115;ASP 233;HIS 289
MET 41;GLN 116
1ei9ASER 115;ASP 233;HIS 289
MET 41;GLN 116
1exwASER 115;ASP 233;HIS 289
MET 41;GLN 116
1fj2ASER 114;ASP 169;HIS 203
LEU 25;GLN 115
1fj2BSER 114;ASP 169;HIS 203
LEU 25;GLN 115

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[2]p.4575-4578
[3]p.23849-23851
[4]p.1142-1143

references
[1]
PubMed ID10551886
JournalJ Biol Chem
Year1999
Volume274
Pages33148-54
AuthorsYeh DC, Duncan JA, Yamashita S, Michel T
TitleDepalmitoylation of endothelial nitric-oxide synthase by acyl-protein thioesterase 1 is potentiated by Ca(2+)-calmodulin.
[2]
CommentsX-ray crystallography (2.25 Angstroms)
PubMed ID10781062
JournalProc Natl Acad Sci U S A
Year2000
Volume97
Pages4573-8
AuthorsBellizzi JJ 3rd, Widom J, Kemp C, Lu JY, Das AK, Hofmann SL, Clardy J
TitleThe crystal structure of palmitoyl protein thioesterase 1 and the molecular basis of infantile neuronal ceroid lipofuscinosis.
Related PDB1eh5,1ei9
[3]
CommentsX-ray crystallography (2.4 Angstroms), catalysis
PubMed ID10801859
JournalJ Biol Chem
Year2000
Volume275
Pages23847-51
AuthorsDas AK, Bellizzi JJ 3rd, Tandel S, Biehl E, Clardy J, Hofmann SL
TitleStructural basis for the insensitivity of a serine enzyme (palmitoyl-protein thioesterase) to phenylmethylsulfonyl fluoride.
Related PDB1exw
[4]
CommentsX-ray crystallography (1.5 Angstroms)
PubMed ID11080636
JournalStructure Fold Des
Year2000
Volume8
Pages1137-46
AuthorsDevedjiev Y, Dauter Z, Kuznetsov SR, Jones TL, Derewenda ZS
TitleCrystal structure of the human acyl protein thioesterase I from a single X-ray data set to 1.5 A.
Related PDB1fj2
[5]
PubMed ID12693927
JournalBiochemistry
Year2003
Volume42
Pages4311-20
AuthorsLinder ME, Deschenes RJ
TitleNew insights into the mechanisms of protein palmitoylation.
[6]
PubMed ID12909364
JournalGene
Year2003
Volume312
Pages271-9
AuthorsGlaser RL, Hickey AJ, Chotkowski HL, Chu-LaGraff Q
TitleCharacterization of Drosophila palmitoyl-protein thioesterase 1.

comments
This enzyme belongs to the palmitoyl-protein thioesterase family.
According to the literature [4], these serine-dependent hydrolases catalyze a two-step reaction, acylation and deacylation, each proceeding through a tetrahedral transition state.
In the initial stage, the interaction of the pair of the residues, Asp169-His203 (PDB; 1fj2), activates the nucleophilic serine residue.
In the acyl-enzyme, the acylated serine moves from the catalytic His, giving room for a water, which makes a nucleophilic attack on the ester bond of the serine during the deacylation.
During the acylation and deacylation, the tetrahedral transient oxyanions are stabilized in a positively charged oxyanion hole, formed by the mainchain amides of Leu25 and Gln115 (PDB; 1fj2) (see [4]).

createdupdated
2002-07-042012-10-05
Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2010)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)

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