InterPro: IPR003016 2-oxo acid dehydrogenase, lipoyl-binding site

The 2-oxo acid dehydrogenase multienzyme complexes [1] from bacterial and eukaryotic sources catalyze the oxidative decarboxylation of 2-oxo acids to the corresponding acyl-CoA. These include:

• Pyruvate dehydrogenase complex (PDC).
• 2-oxoglutarate dehydrogenase complex (OGDC).
• Branched-chain 2-oxo acid dehydrogenase complex (BCOADC).

These three complexes share a common architecture: they are composed of multiple copies of three component enzymes - E1, E2 and E3. E1 is a thiamine pyrophosphate-dependent 2-oxo acid dehydrogenase, E2 a dihydrolipamide acyltransferase, and E3 an FAD-containing dihydrolipamide dehydrogenase.

E2 acyltransferases have an essential cofactor, lipoic acid, which is covalently bound via a amide linkage to a lysine group. The E2 components of OGCD and BCOACD bind a single lipoyl group, while those of PDC bind either one (in yeast and in Bacillus), two (in mammals), or three (in Azotobacter and in Escherichia coli) lipoyl groups [2].

In addition to the E2 components of the three enzymatic complexes described above, a lipoic acid cofactor is also found in the following proteins:

• H-protein of the glycine cleavage system (GCS) [3]. GCS is a multienzyme complex of four protein components, which catalyzes the degradation of glycine. H protein shuttles the methylamine group of glycine from the P protein to the T protein. H-protein from either prokaryotes or eukaryotes binds a single lipoic group.
• Mammalian and yeast pyruvate dehydrogenase complexes differ from that of other sources, in that they contain, in small amounts, a protein of unknown function - designated protein X or component X. Its sequence is closely related to that of E2 subunits and seems to bind a lipoic group [4].
• Fast migrating protein (FMP) (gene acoC) from Ralstonia eutropha (Alcaligenes eutrophus) [5]. This protein is most probably a dihydrolipamide acyltransferase involved in acetoin metabolism.

This signature contains the lipoyl-binding lysine residue. The domain surronding this site is evolutionary related to that around the biotin-binding lysine residue of biotin requiring enzymes.