Citrate synthase, eukaryotic-type (IPR010109)

Short name: Citrate_synthase_euk

Overlapping homologous superfamilies

Family relationships


Citrate synthase EC: 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 includes both mitochondrial and peroxisomal forms of citrate synthase. Peroxisomal forms of the enzyme, recognised by the C-terminal targeting motif SKL, act in the glyoxylate cycle. Eukaryotic homologues include a Tetrahymena thermophila citrate synthase that doubles as a filament protein, a putative citrate synthase from Plasmodium falciparum (no TCA cycle), and a methylcitrate synthase from Emericella nidulans (Aspergillus nidulans).

GO terms

Biological Process

GO:0006101 citrate metabolic process

Molecular Function

GO:0004108 citrate (Si)-synthase activity

Cellular Component

No terms assigned in this category.

Contributing signatures

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