EzCatDB: S00179
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DB codeS00179
RLCP classification1.14.36110.975 : Hydrolysis
CATH domainDomain 13.10.129.10 : Thiol Ester Dehydrase; Chain ACatalytic domain
E.C.3.1.2.23

CATH domainRelated DB codes (homologues)
3.10.129.10 : Thiol Ester Dehydrase; Chain AS00180

Enzyme Name
UniProtKBKEGG

P56653
Protein name4-hydroxybenzoyl-CoA thioesterase4-hydroxybenzoyl-CoA thioesterase
SynonymsEC 3.1.2.23
PfamPF03061 (4HBT)
[Graphical view]

KEGG pathways
MAP codePathways
MAP006232,4-Dichlorobenzoate degradation

UniProtKB:Accession NumberP56653
Entry name4HBT_PSEUC
Activity4-hydroxybenzoyl-CoA + H(2)O = 4- hydroxybenzoate + CoA.
SubunitHomotetramer.
Subcellular location
Cofactor

Compound table: links to PDB-related databases & PoSSuM

SubstratesProducts
KEGG-idC02949C00001C00010C00156
Compound4-Hydroxybenzoyl-CoAH2OCoA4-Hydroxybenzoate
Typeamine group,aromatic ring (only carbon atom),carbohydrate,nucleotide,peptide/protein,sulfide groupH2Oamine group,carbohydrate,nucleotide,peptide/protein,sulfhydryl grouparomatic ring (only carbon atom),carboxyl group
ChEBI15500
15377
15346
30763
PubChem439862
168718
962
22247451
87642
6816
3702506
135
            
1bvqAUnbound UnboundUnbound
1lo7AAnalogue:4CO UnboundUnbound
1lo8AAnalogue:4CA UnboundUnbound
1lo9ABound:BCA UnboundUnbound

Active-site residues
resource
literature [2], [3], [4]
pdbCatalytic residuesMain-chain involved in catalysiscomment
           
1bvqAASP 17;ASP 32
TYR 24
 
1lo7AASP 17;ASP 32
TYR 24
 
1lo8AASP 17;ASP 32
TYR 24
 
1lo9A      ;ASP 32
TYR 24
mutant D17N

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[1]p.33576-33578
[2]Fig.72
[3]p.27474-27476

references
[1]
CommentsX-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
Medline ID99057924
PubMed ID9837940
JournalJ Biol Chem
Year1998
Volume273
Pages33572-9
AuthorsBenning MM, Wesenberg G, Liu R, Taylor KL, Dunaway-Mariano D, Holden HM
TitleThe three-dimensional structure of 4-hydroxybenzoyl-CoA thioesterase from Pseudomonas sp. Strain CBS-3.
Related PDB1bvq
Related UniProtKBP56653
[2]
PubMed ID12220180
JournalBiochemistry
Year2002
Volume41
Pages11152-60
AuthorsZhuang Z, Song F, Zhang W, Taylor K, Archambault A, Dunaway-Mariano D, Dong J, Carey PR
TitleKinetic, Raman, NMR, and site-directed mutagenesis studies of the Pseudomonas sp. strain CBS3 4-hydroxybenzoyl-CoA thioesterase active site.
[3]
CommentsX-ray crystallography
PubMed ID11997398
JournalJ Biol Chem
Year2002
Volume277
Pages27468-76
AuthorsThoden JB, Holden HM, Zhuang Z, Dunaway-Mariano D
TitleX-ray crystallographic analyses of inhibitor and substrate complexes of wild-type and mutant 4-hydroxybenzoyl-CoA thioesterase.
Related PDB1lo7,1lo8,1lo9
[4]
PubMed ID12907670
JournalJ Biol Chem
Year2003
Volume278
Pages43709-16
AuthorsThoden JB, Zhuang Z, Dunaway-Mariano D, Holden HM
TitleThe structure of 4-hydroxybenzoyl-CoA thioesterase from arthrobacter sp. strain SU.
Related PDB1q4s,1q4t,1q4u

comments
Originally, this data was for E.C. 3.8.1.6. However, the Swiss-prot data and literature suggest that the function must be for E.C. 3.1.2.23.
The active site residues are contributed by the second subunit of the homodimer or homotetramer [1].
Asp17 serves as the putative base catalyst [1]. OD1 atom of Asp17 is located at 6.0 A from the substrate thioester carbon, providing the adequate space between the substrate and Asp17 for the positioning of a water molecule for nucleophilic attack during the catalysis. The backbone amide atom of Ile61 is within hydrogen bonding distance to the thioester oxygen, whose interaction could result in the polarization of the carbonyl C=O bond, thereby activating the carbonyl carbon for nucleophilic attack, and in the stabilization of the developing oxyanion transition state [1]. On the other hand, mainchain amide group of Tyr24 plays this role, according to the literature ([3] & [4]).
According to the literature [2] and [3], the catalytic role played by Asp17 seems to be a nucleophile which makes an attack directly on the acyl carbon of the thioester substrate to form an anhydride enzyme intermediate. However, a question still remains. If the catalytic reaction proceeds via the intermediate, then the water nucleophile binds and attacks at the carbonyl carbon.
According to the literature [4], although the homodimer structures with ligand of its homologous enzyme have been determined, the active site is not the same as that of this enzyme (see PDB;1q4s, 1q4t, 1q4u). However, comparison with the structure suggests that Asp32 may act as a general base, which activate a water, since Glu73 of the counterpart enzyme seems to play the role (see [4]).
Taken together, the catalytic reaction proceeds as follows:
(1) Mainchain amide group of Tyr24 polarizes and activates the carbonyl oxygen of thioester for nucleophilic attack. (This suggests dissociative reaction.)
(2) Asp17 acts as a nucleophile, which attacks on the thioester carbonyl carbon, leading to formation of a tetrahedral transition-state. The oxyanion of the transition-state is stabilized by the mainchain amide of Tyr24.
(3) This collapses, leading to the formation of acyl intermediate and release of CoA. (The leaving sulfur atom of CoA might be protonated by Asp32 from the next subunit.)
(4) Asp32 from the next subunit acts as a general base, which activates a water moleucle.
(5) The activated water makes a nucleophilic attack on the acyl intermediate, completing the reaction.

createdupdated
2002-07-042009-02-26


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