Conservation of a glutamate residue in ATP-citrate lyase and succinyl-CoA synthetase

Succinyl-CoA synthetase (SCS), the enzyme that catalyzes the only substrate-level phosphorylation in the citrate cycle, is the prototype for a family of ADP- or GDP-forming acyl-CoA synthetases that includes ATP-citrate lyase (ACLY) [1]. These enzymes catalyze the formation of a thioester bond between an organic acid and CoA, using the energy of nucleotide triphosphate (NTP) and in the presence of magnesium ions. A histidine residue is transiently phosphorylated during catalysis leading to the proposed catalytic mechanism: where E represents the enzyme; – , a covalent bond; and ∙ , noncovalent interactions. For SCS, the carboxylate is succinate; for ACLY, it is citrate and there is fourth step in which citryl-CoA is cleaved to form acetyl-CoA and oxaloacetate. A residue