DB code: S00350

RLCP classification 1.14.30000.10 : Hydrolysis
CATH domain 3.40.50.1820 : Rossmann fold Catalytic domain
E.C. 3.1.2.22
CSA 1eh5
M-CSA 1eh5
MACiE

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

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam MEROPS
P45478 Palmitoyl-protein thioesterase 1
PPT-1
EC 3.1.2.22
Palmitoyl-protein hydrolase 1
NP_776579.1 (Protein)
NM_174154.2 (DNA/RNA sequence)
PF02089 (Palm_thioest)
[Graphical View]
O75608 Acyl-protein thioesterase 1
EC 3.1.2.-
Lysophospholipase 1
Lysophospholipase I
NP_006321.1 (Protein)
NM_006330.2 (DNA/RNA sequence)
PF02230 (Abhydrolase_2)
[Graphical View] 		S09.026 (Serine)

KEGG enzyme name
palmitoyl[protein] hydrolase
palmitoyl-protein thioesterase
palmitoyl-(protein) hydrolase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P45478 PPT1_BOVIN Palmitoyl-protein + H(2)O = palmitate + protein. Lysosome.
O75608 LYPA1_HUMAN Palmitoyl-protein + H(2)O = palmitate + protein. Homodimer. Cytoplasm (By similarity).

KEGG Pathways
Map code Pathways E.C.
MAP00062 Fatty acid elongation in mitochondria

Compound table
Substrates Products Intermediates
KEGG-id C06412 C00001 C00249 C00017 I00147 I00085 I00086
E.C.
Compound Palmitoyl-protein H2O Palmitate Protein Peptidyl-Ser-tetrahedral intermediate (with previous thioester) Acyl-enzyme(Peptidyl-Ser-acyl group) Peptidyl-Ser-tetrahedral-intermediate
Type lipid,peptide/protein H2O fatty acid peptide/protein
ChEBI 15377
 15377
 		15756
 15756
PubChem 22247451
 962
 22247451
 962
 		985
 985
1eh5A Unbound Unbound Unbound Unbound Intermediate-bound:PLM Unbound
1ei9A Unbound Unbound Unbound Unbound Unbound Unbound
1exwA Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:HDS
1fj2A Unbound Unbound Unbound Unbound Unbound Unbound
1fj2B Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1eh5A SER 115;ASP 233;HIS 289 MET 41;GLN 116
1ei9A SER 115;ASP 233;HIS 289 MET 41;GLN 116
1exwA SER 115;ASP 233;HIS 289 MET 41;GLN 116
1fj2A SER 114;ASP 169;HIS 203 LEU 25;GLN 115
1fj2B SER 114;ASP 169;HIS 203 LEU 25;GLN 115

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[2]
p.4575-4578
[3]
p.23849-23851
[4]
p.1142-1143

References
[1]
Resource
Comments
Medline ID
PubMed ID 10551886
Journal J Biol Chem
Year 1999
Volume 274
Pages 33148-54
Authors Yeh DC, Duncan JA, Yamashita S, Michel T
Title Depalmitoylation of endothelial nitric-oxide synthase by acyl-protein thioesterase 1 is potentiated by Ca(2+)-calmodulin.
Related PDB
Related UniProtKB
[2]
Resource
Comments X-ray crystallography (2.25 Angstroms)
Medline ID
PubMed ID 10781062
Journal Proc Natl Acad Sci U S A
Year 2000
Volume 97
Pages 4573-8
Authors Bellizzi JJ 3rd, Widom J, Kemp C, Lu JY, Das AK, Hofmann SL, Clardy J
Title The crystal structure of palmitoyl protein thioesterase 1 and the molecular basis of infantile neuronal ceroid lipofuscinosis.
Related PDB 1eh5 1ei9
Related UniProtKB
[3]
Resource
Comments X-ray crystallography (2.4 Angstroms), catalysis
Medline ID
PubMed ID 10801859
Journal J Biol Chem
Year 2000
Volume 275
Pages 23847-51
Authors Das AK, Bellizzi JJ 3rd, Tandel S, Biehl E, Clardy J, Hofmann SL
Title Structural basis for the insensitivity of a serine enzyme (palmitoyl-protein thioesterase) to phenylmethylsulfonyl fluoride.
Related PDB 1exw
Related UniProtKB
[4]
Resource
Comments X-ray crystallography (1.5 Angstroms)
Medline ID
PubMed ID 11080636
Journal Structure Fold Des
Year 2000
Volume 8
Pages 1137-46
Authors Devedjiev Y, Dauter Z, Kuznetsov SR, Jones TL, Derewenda ZS
Title Crystal structure of the human acyl protein thioesterase I from a single X-ray data set to 1.5 A.
Related PDB 1fj2
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 12693927
Journal Biochemistry
Year 2003
Volume 42
Pages 4311-20
Authors Linder ME, Deschenes RJ
Title New insights into the mechanisms of protein palmitoylation.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 12909364
Journal Gene
Year 2003
Volume 312
Pages 271-9
Authors Glaser RL, Hickey AJ, Chotkowski HL, Chu-LaGraff Q
Title Characterization of Drosophila palmitoyl-protein thioesterase 1.
Related PDB
Related UniProtKB

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]).

Created Updated
2002-07-04 2012-10-05