EzCatDB S00350

DB code

S00350

RLCP classification

1.14.30000.10 : Hydrolysis

CATH domain

Domain 1

3.40.50.1820 : Rossmann fold

Catalytic domain

E.C.

3.1.2.22

CSA

1eh5

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

Enzyme Name

UniProtKB

KEGG

P45478

O75608

Protein name

Palmitoyl-protein thioesterase 1

Acyl-protein thioesterase 1

palmitoyl[protein] hydrolase
palmitoyl-protein thioesterase
palmitoyl-(protein) hydrolase

Synonyms

PPT-1
EC 3.1.2.22
Palmitoyl-protein hydrolase 1

EC 3.1.2.-
Lysophospholipase 1
Lysophospholipase I

RefSeq

NP_776579.1 (Protein)
NM_174154.2 (DNA/RNA sequence)

NP_006321.1 (Protein)
NM_006330.2 (DNA/RNA sequence)

MEROPS

S09.026 (Serine)

Pfam

PF02089 (Palm_thioest)
[Graphical view]

PF02230 (Abhydrolase_2)
[Graphical view]

KEGG pathways

MAP code

Pathways

MAP00062

Fatty acid elongation in mitochondria

UniProtKB:Accession Number

P45478

O75608

Entry name

PPT1_BOVIN

LYPA1_HUMAN

Activity

Palmitoyl-protein + H(2)O = palmitate + protein.

Subunit

Homodimer.

Subcellular location

Lysosome.

Cytoplasm (By similarity).

Cofactor

Compound table: links to PDB-related databases & PoSSuM

Substrates

Products

intermediates

KEGG-id

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

PubChem

985

Unbound

Intermediate-bound:PLM

Unbound

1ei9A

Unbound

1exwA

Unbound

Intermediate-analogue:HDS

1fj2A

Unbound

1fj2B

Unbound

Active-site residues

pdb

Catalytic residues

Main-chain involved in catalysis

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]

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.

[2]

Comments

X-ray crystallography (2.25 Angstroms)

PubMed ID

10781062

Journal

Proc Natl Acad Sci U S A

Year

2000

Volume

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

[3]

Comments

X-ray crystallography (2.4 Angstroms), catalysis

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

[4]

Comments

X-ray crystallography (1.5 Angstroms)

PubMed ID

11080636

Journal

Structure Fold Des

Year

2000

Volume

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

[5]

PubMed ID

12693927

Journal

Biochemistry

Year

2003

Volume

Pages

4311-20

Authors

Linder ME, Deschenes RJ

Title

New insights into the mechanisms of protein palmitoylation.

[6]

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.

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

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 2008)
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)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )