Proposed Mechanism for the Condensation Reaction of Citrate Synthase: 1.9-Å Structure of the Ternary Complex with Oxaloacetate and Carboxymethyl Coenzyme A

Mihail Karpusas, Bruce Branchaud, S. James Remington

Research output: Contribution to journalArticle

107 Scopus citations

Abstract

The crystal structure of the ternary complex citrate synthase-oxaloacetate-carboxymethyl coenzyme A has been solved to a resolution of 1.9 Å and refined to a conventional crystallographic R factor of 0.185. The structure resembles a proposed transition state of the condensation reaction and suggests that the condensation reaction proceeds through a neutral enol rather than an enolate intermediate. A mechanism for the condensation reaction is proposed which involves the participation of three key catalytic groups (Asp 375, His 274, and His 320) in two distinct steps. The proposed mechanism invokes concerted general acid-base catalysis twice to explain both the energetics of the reaction and the experimentally observed inversion of stereochemistry at the attacking carbon atom.

Original languageEnglish (US)
Pages (from-to)2213-2219
Number of pages7
JournalBiochemistry
Volume29
Issue number9
DOIs
StatePublished - Mar 1 1990

ASJC Scopus subject areas

  • Biochemistry

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