Citrate synthase catalyses the condensation between the carbonyl of oxaloacetate and the acetyl methyl group of acetyl CoA. A reaction considered to be the first step in the citric acid cycle (Krebs cycle) proper.
The product of this reaction, citryl-CoA, remains tightly bound to the enzyme and is hydrolysed to citrate and CoA in a separate chemical step that nevertheless uses the same catalytic residues. Conformational changes of the enzyme during the reaction are believed to be important in the catalytic mechanism.
Although most studies have been done on pig citrate synthase, but the structural equivalence of the amino acid residues implicated in catalysis for the Pyrococcus protein implies that the mechanism proceeds via the same acid/base catalytic process.
Defined by 5 residues: SER:A-244HIS:A-274HIS:A-320ARG:A-329ASP:A-375