<p>Citrate synthase <db_xref db="EC" dbkey="2.3.3.1"/> is a member of a small family of enzymes that can directly form a carbon-carbon bond without the presence of metal ion cofactors. It catalyses the first reaction in the Krebs' cycle, namely the conversion of oxaloacetate and acetyl-coenzyme A into citrate and coenzyme A. This reaction is important for energy generation and for carbon assimilation. The reaction proceeds via a non-covalently bound citryl-coenzyme A intermediate in a 2-step process (aldol-Claisen condensation followed by the hydrolysis of citryl-CoA). </p><p>Citrate synthase enzymes are found in two distinct structural types: type I enzymes (found in eukaryotes, Gram-positive bacteria and archaea) form homodimers and have shorter sequences than type II enzymes, which are found in Gram-negative bacteria and are hexameric in structure. In both types, the monomer is composed of two domains: a large alpha-helical domain consisting of two structural repeats, where the second repeat is interrupted by a small alpha-helical domain. The cleft between these domains forms the active site, where both citrate and acetyl-coenzyme A bind. The enzyme undergoes a conformational change upon binding of the oxaloacetate ligand, whereby the active site cleft closes over in order to form the acetyl-CoA binding site [<cite idref="PUB00042604"/>]. The energy required for domain closure comes from the interaction of the enzyme with the substrate. Type II enzymes possess an extra N-terminal beta-sheet domain, and some type II enzymes are allosterically inhibited by NADH [<cite idref="PUB00042605"/>].</p><p>This entry represents the large alpha-helical domain from type I and II citrate synthase enzymes, as well as a homolgous domain found in the related enzyme 2-methylcitrate synthase. 2-methylcitrate (<db_xref db="EC" dbkey="2.3.3.5"/>) synthase catalyses the conversion of oxaloacetate and propanoyl-CoA into (2R,3S)-2-hydroxybutane-1,2,3-tricarboxylate and coenzyme A. This enzyme is induced during bacterial growth on propionate, while type II hexameric citrate synthase is constitutive [<cite idref="PUB00013490"/>]. </p>