cd06849: lipoyl_attach_2-OADH_E2 (This model is not part of the current CDD release)
lipoyl attachment domain found in the E2 component of 2-oxoacid dehydrogenase (2-OADH) family proteins
The lipoyl attachment domain is a protein module that typically consists of a flattened beta-barrel structure, featuring a conserved lysine residue located at the tip of a protruding beta-turn within one of the beta-sheets. This lysine residue serves as the attachment point for lipoic acid, a vital cofactor for enzymes in metabolic pathways, such as the pyruvate dehydrogenase complex. This domain acts as a "swinging arm," with its proline-alanine-rich linker, to shuttle reaction intermediates between active sites within large enzyme complexes. This process is essential for the function of several metabolic pathways, enabling substrate channeling and promoting catalytic efficiency by allowing the cofactor to reach different active sites within the complex. The lipoyl attachment domain shares a similar fold and binding mechanism with the biotin attachment domain, another essential protein module for biotin-dependent enzymes. The model corresponds to the lipoyl attachment domain found in the E2 component of 2-oxoacid dehydrogenase (2-OADH) family proteins. The 2-OADH family comprises multi-enzyme complexes that catalyze the oxidative decarboxylation of 2-oxoacids, linking carbohydrate, lipid, and amino acid metabolism to central energy pathways like the citric acid cycle. Key members include the pyruvate dehydrogenase complex (PDC), the branched-chain 2-oxoacid dehydrogenase complex (BCOADC), and the 2-oxoglutarate dehydrogenase complex (OGDC). PDC links glycolysis to the citric acid cycle by converting pyruvate to acetyl-CoA. BCOADC oxidatively decarboxylates the 2-oxoacids derived from the transamination of branched-chain amino acids (valine, leucine, isoleucine). OGDC catalyzes the conversion of 2-oxoglutarate to succinyl-CoA within the citric acid cycle. All three complexes in the family share a common architecture and are composed of multiple copies of three component enzymes: E1 (2-oxoacid decarboxylase), E2 (dihydrolipoyl acyltransferase), and E3 (dihydrolipoamide dehydrogenase). The E1 component is the thiamine pyrophosphate (TPP)-dependent enzyme that initiates the decarboxylation. The E2 component forms the structural core of the complex, containing the lipoyl cofactor that transfers the acyl group. The E3 component is a FAD-containing enzyme that regenerates the oxidized lipoyl cofactor.
Jiyao W et al.(2023). "The conserved domain database in 2023.",