InterPro domain: IPR011603

2-oxoglutarate dehydrogenase is a key enzyme in the TCA cycle, converting 2-oxoglutarate, coenzyme A and NAD(+) to succinyl-CoA, NADH and carbon dioxide [ 1 ]. This activity of this enzyme is tightly regulated and it is a major determinant of the metabolic flux through the TCA cycle. This enzyme is composed of multiple copies of three different subunits: 2-oxoglutarate dehydrogenase (E1), dihydrolipoamide succinyltransferase (E2) and lipoamide dehydrogenase (E3) which is often shared with similar enzymes such as pyruvate dehydrogenase [ 2 ]. The E2 component forms a large multimeric core which binds the peripheral E1 and E3 subunits. The substrate is transferred between the active sites of the different subunits by a lipoyl moiety, bound to a lysine residue from the E2 polypeptide.

The E1 subunit of 2-oxoglutarate dehydrogenase catalyses the decarboxylation of this compound in a thiamine pyrophosphate-dependent manner, transferring the resultant succinyl group onto the liposyl moiety bound to the E2 subunit. The E1 ortholog from Corynebacterium glutamicum (Brevibacterium flavum) is unusual in having an N-terminal extension that resembles the E2 component of 2-oxoglutarate dehydrogenase enzyme.

1. Alpha-ketoglutarate dehydrogenase: a target and generator of oxidative stress. Philos. Trans. R. Soc. Lond., B, Biol. Sci. 360, 2335-45
2. 2-Oxo acid dehydrogenase multienzyme complexes. The central role of the lipoyl domain. Biol. Chem. 378, 617-34