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| CATH domain | Related DB codes (homologues) |
|---|
| 3.10.129.10 : Thiol Ester Dehydrase; Chain A | S00180 |
| KEGG pathways | | MAP code | Pathways |
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| MAP00623 | 2,4-Dichlorobenzoate degradation |
| UniProtKB:Accession Number | P56653 |
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| Entry name | 4HBT_PSEUC |
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| Activity | 4-hydroxybenzoyl-CoA + H(2)O = 4- hydroxybenzoate + CoA. |
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| Subunit | Homotetramer. |
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| Subcellular location |
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| Cofactor |
|
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| Compound table: links to PDB-related databases & PoSSuM |
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| Substrates | Products |
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| KEGG-id | C02949 | C00001 | C00010 | C00156 |
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| 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
|
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| | | | | | | | | | | | |
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| 1bvqA |  |  |  |  |  |  |  | Unbound | | Unbound | Unbound |
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| 1lo7A | | | | | | | | Analogue:4CO | | Unbound | Unbound |
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| 1lo8A | | | | | | | | Analogue:4CA | | Unbound | Unbound |
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| 1lo9A | | | | | | | | Bound:BCA | | Unbound | Unbound |
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| 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] |
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| Comments | X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS). |
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| Medline ID | 99057924 |
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| PubMed ID | 9837940 |
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| Journal | J Biol Chem |
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| Year | 1998 |
|---|
| Volume | 273 |
|---|
| Pages | 33572-9 |
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| Authors | Benning MM, Wesenberg G, Liu R, Taylor KL, Dunaway-Mariano D, Holden HM |
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| Title | The three-dimensional structure of 4-hydroxybenzoyl-CoA thioesterase from Pseudomonas sp. Strain CBS-3. |
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| Related PDB | 1bvq |
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| Related UniProtKB | P56653 |
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| [2] |
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| PubMed ID | 12220180 |
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| Journal | Biochemistry |
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| Year | 2002 |
|---|
| Volume | 41 |
|---|
| Pages | 11152-60 |
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| Authors | Zhuang Z, Song F, Zhang W, Taylor K, Archambault A, Dunaway-Mariano D, Dong J, Carey PR |
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| Title | Kinetic, Raman, NMR, and site-directed mutagenesis studies of the Pseudomonas sp. strain CBS3 4-hydroxybenzoyl-CoA thioesterase active site. |
|---|
| [3] |
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| Comments | X-ray crystallography |
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| PubMed ID | 11997398 |
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| Journal | J Biol Chem |
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| Year | 2002 |
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| Volume | 277 |
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| Pages | 27468-76 |
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| Authors | Thoden JB, Holden HM, Zhuang Z, Dunaway-Mariano D |
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| Title | X-ray crystallographic analyses of inhibitor and substrate complexes of wild-type and mutant 4-hydroxybenzoyl-CoA thioesterase. |
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| Related PDB | 1lo7,1lo8,1lo9 |
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| [4] |
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| PubMed ID | 12907670 |
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| 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 |
|---|
| 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.
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| created | updated |
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| 2002-07-04 | 2009-02-26 |
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