1lo9
From Proteopedia
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'''X-ray crystal structure of 4-hydroxybenzoyl CoA thioesterase mutant D17N complexed with 4-hydroxybenzoyl CoA''' | '''X-ray crystal structure of 4-hydroxybenzoyl CoA thioesterase mutant D17N complexed with 4-hydroxybenzoyl CoA''' | ||
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[[Category: Thoden, J B.]] | [[Category: Thoden, J B.]] | ||
[[Category: Zhuang, Z.]] | [[Category: Zhuang, Z.]] | ||
| - | [[Category: | + | [[Category: Catalytic mechanism]] |
| - | [[Category: | + | [[Category: Hot dog fold]] |
| - | [[Category: | + | [[Category: Thioesterase]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 00:06:40 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 21:06, 2 May 2008
X-ray crystal structure of 4-hydroxybenzoyl CoA thioesterase mutant D17N complexed with 4-hydroxybenzoyl CoA
Overview
The metabolic pathway by which 4-chlorobenzoate is degraded to 4-hydroxybenzoate in the soil-dwelling microbe Pseudomonas sp. strain CBS-3 consists of three enzymes including 4-hydroxybenzoyl-CoA thioesterase. The structure of the unbound form of this thioesterase has been shown to contain the so-called "hot dog" fold with a large helix packed against a five-stranded anti-parallel beta-sheet. To address the manner in which the enzyme accommodates the substrate within the active site, two inhibitors have been synthesized, namely 4-hydroxyphenacyl-CoA and 4-hydroxybenzyl-CoA. Here we describe the structural analyses of the enzyme complexed with these two inhibitors determined and refined to 1.5 and 1.8 A resolution, respectively. These studies indicate that only one protein side chain, Ser(91), participates directly in ligand binding. All of the other interactions between the protein and the inhibitors are mediated through backbone peptidic NH groups, carbonyl oxygens, and/or solvents. The structures of the enzyme-inhibitor complexes suggest that both a hydrogen bond and the positive end of a helix dipole moment serve to polarize the electrons away from the carbonyl carbon of the acyl group, thereby making it more susceptible to nucleophilic attack. Additionally, these studies demonstrate that the carboxylate group of Asp(17) is approximately 3.2 A from the carbonyl carbon of the acyl group. To address the role of Asp(17), the structure of the site-directed mutant protein D17N with bound substrate has also been determined. Taken together, these investigations suggest that the reaction mechanism may proceed through an acyl enzyme intermediate.
About this Structure
1LO9 is a Single protein structure of sequence from Pseudomonas sp.. Full crystallographic information is available from OCA.
Reference
X-ray crystallographic analyses of inhibitor and substrate complexes of wild-type and mutant 4-hydroxybenzoyl-CoA thioesterase., Thoden JB, Holden HM, Zhuang Z, Dunaway-Mariano D, J Biol Chem. 2002 Jul 26;277(30):27468-76. Epub 2002 May 7. PMID:11997398 Page seeded by OCA on Sat May 3 00:06:40 2008
