Domain

Citrate synthase-like, large alpha subdomain (IPR016142)

Short name: Citrate_synth-like_lrg_a-sub

Domain relationships

None.

Description

Citrate synthase EC: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).

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 [PMID: 15147839]. 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 [PMID: 17087502].

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 (EC: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 [PMID: 9579066].

GO terms

Biological Process

GO:0044262 cellular carbohydrate metabolic process

Molecular Function

GO:0046912 transferase activity, transferring acyl groups, acyl groups converted into alkyl on transfer

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
GENE3D