DB code: S00179

RLCP classification 1.14.36110.975 : Hydrolysis
CATH domain 3.10.129.10 : Thiol Ester Dehydrase; Chain A Catalytic domain
E.C. 3.1.2.23
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
3.10.129.10 : Thiol Ester Dehydrase; Chain A S00180

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Pfam
P56653 4-hydroxybenzoyl-CoA thioesterase
EC 3.1.2.23
PF03061 (4HBT)
[Graphical View]

KEGG enzyme name
4-hydroxybenzoyl-CoA thioesterase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P56653 4HBT_PSEUC 4-hydroxybenzoyl-CoA + H(2)O = 4- hydroxybenzoate + CoA. Homotetramer.

KEGG Pathways
Map code Pathways E.C.
MAP00623 2,4-Dichlorobenzoate degradation

Compound table
Substrates Products Intermediates
KEGG-id C02949 C00001 C00010 C00156
E.C.
Compound 4-Hydroxybenzoyl-CoA H2O CoA 4-Hydroxybenzoate
Type amine group,aromatic ring (only carbon atom),carbohydrate,nucleotide ,peptide/protein,sulfide group H2O amine group,carbohydrate,nucleotide ,peptide/protein,sulfhydryl group aromatic ring (only carbon atom),carboxyl group
ChEBI 15500
15377
15346
30763
PubChem 168718
439862
22247451
962
6816
87642
135
3702506
1bvqA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound
1lo7A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:4CO Unbound Unbound
1lo8A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:4CA Unbound Unbound
1lo9A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:BCA Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [2], [3], [4]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1bvqA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 17;ASP 32 TYR 24
1lo7A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 17;ASP 32 TYR 24
1lo8A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 17;ASP 32 TYR 24
1lo9A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ;ASP 32 TYR 24 mutant D17N

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[1]
p.33576-33578
[2]
Fig.7 2
[3]
p.27474-27476

References
[1]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
Medline ID 99057924
PubMed ID 9837940
Journal J Biol Chem
Year 1998
Volume 273
Pages 33572-9
Authors Benning MM, Wesenberg G, Liu R, Taylor KL, Dunaway-Mariano D, Holden HM
Title The three-dimensional structure of 4-hydroxybenzoyl-CoA thioesterase from Pseudomonas sp. Strain CBS-3.
Related PDB 1bvq
Related UniProtKB P56653
[2]
Resource
Comments
Medline ID
PubMed ID 12220180
Journal Biochemistry
Year 2002
Volume 41
Pages 11152-60
Authors Zhuang Z, Song F, Zhang W, Taylor K, Archambault A, Dunaway-Mariano D, Dong J, Carey PR
Title Kinetic, Raman, NMR, and site-directed mutagenesis studies of the Pseudomonas sp. strain CBS3 4-hydroxybenzoyl-CoA thioesterase active site.
Related PDB
Related UniProtKB
[3]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 11997398
Journal J Biol Chem
Year 2002
Volume 277
Pages 27468-76
Authors Thoden JB, Holden HM, Zhuang Z, Dunaway-Mariano D
Title X-ray crystallographic analyses of inhibitor and substrate complexes of wild-type and mutant 4-hydroxybenzoyl-CoA thioesterase.
Related PDB 1lo7 1lo8 1lo9
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 12907670
Journal J Biol Chem
Year 2003
Volume 278
Pages 43709-16
Authors Thoden JB, Zhuang Z, Dunaway-Mariano D, Holden HM
Title The structure of 4-hydroxybenzoyl-CoA thioesterase from arthrobacter sp. strain SU.
Related PDB 1q4s 1q4t 1q4u
Related UniProtKB

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.

Created Updated
2002-07-04 2009-02-26