InterPro domain: IPR005810

There are four different enzymes that share a similar catalytic mechanism which involves the phosphorylation by ATP (or GTP) of a specific histidine residue in the active site. These enzymes are

• ATP citrate-lyase ( 4.1.3.8 ) [ 1 ], the primary enzyme responsible for the synthesis of cytosolic acetyl-CoA in many tissues, catalyzes the formation of acetyl-CoA and oxaloacetate from citrate and CoA with the concomitant hydrolysis of ATP to ADP and phosphate. ATP-citrate lyase is a tetramer of identical subunits.
• Succinyl-CoA ligase (GDP-forming) ( 6.2.1.4 ) [ 2 ] is a mitochondrial enzyme that catalyzes the substrate level phosphorylation step of the tricarboxylic acid cycle: the formation of succinyl-CoA from succinate with a concomitant hydrolysis of GTP to GDP and phosphate. This enzyme is a dimer composed of an alpha and a beta subunits.
• Succinyl-CoA ligase (ADP-forming) ( 6.2.1.5 ) [ 3 ] is a bacterial enzyme that during aerobic metabolism functions in the citric acid cycle, coupling the hydrolysis of succinyl-CoA to the synthesis of ATP. It can also function in the other direction for anabolic purposes. This enzyme is a tetramer composed of two alpha and two beta subunits.
• Malate-CoA ligase ( 6.2.1.9 ) (malyl-CoA synthetase) [ 4 ], is a bacterial enzyme that forms malyl-CoA from malate and CoA with the concomitant hydrolysis of ATP to ADP and phosphate. Malate-CoA ligase is composed of two different subunits.

This entry describes succinyl-CoA synthetase alpha subunits, but does not discriminate between GTP-specific and ATP-specific reactions. ATP citrate lyases appear to form an outgroup, and are not included in this entry.

1. Cloning and expression of a human ATP-citrate lyase cDNA. Eur. J. Biochem. 204, 491-9
2. Cloning, characterization, and expression of the beta subunit of pig heart succinyl-CoA synthetase. Protein Sci. 2, 1255-62
3. Primary structure of the succinyl-CoA synthetase of Escherichia coli. Biochemistry 24, 6245-52
4. Genetics of the serine cycle in Methylobacterium extorquens AM1: identification, sequence, and mutation of three new genes involved in C1 assimilation, orf4, mtkA, and mtkB. J. Bacteriol. 176, 7398-404