Pathways & interactions
Citrate synthase-like, small alpha subdomain (IPR016143)
Short name: Citrate_synth-like_sm_a-sub
- Citrate synthase (IPR002020)
- Citrate synthase, eukaryotic-type (IPR010109)
- Citrate synthase, type I (IPR010953)
- 2-methylcitrate synthase/citrate synthase type I (IPR011278)
- ATP-citrate synthase (IPR014608)
- Citrate synthase-like, large alpha subdomain (IPR016142)
- Citrate synthase, bacterial-type (IPR024176)
- Citrate synthase superfamily (IPR036969)
Citrate synthase EC:18.104.22.168 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 small alpha-helical domain from type I and II citrate synthase enzymes, as well as a homolgous domain found in the related enzyme ATP citrate synthase. ATP citrate synthase (EC:22.214.171.124) (also known as ATP citrate lyase) catalyses the MgATP-dependent, CoA-dependent cleavage of citrate into oxaloacetate and acetyl-CoA, a key step in the reductive tricarboxylic acid pathway of CO2 assimilation used by a variety of autotrophic bacteria and archaea to fix carbon dioxide [PMID: 16952946]. ATP citrate synthase is composed of two distinct subunits. In eukaryotes, ATP citrate synthase is a homotetramer of a single large polypeptide, and is used to produce cytosolic acetyl-CoA from mitochondrial-produced citrate [PMID: 16007201].
- G3DSA:126.96.36.199 (G3DSA:188.8.131.52)