InterPro domain: IPR000089

The biotin/lipoyl attachment domain has a conserved lysine residue that binds biotin or lipoic acid. The 80 residues surrounding the biotinyl-binding lysine residue display some sequence similarity to that around the lipoyl-binding lysine residue. Biotin plays a catalytic role in some carboxyl transfer reactions and is covalently attached, via an amide bond, to a lysine residue in enzymes requiring this coenzyme [ 1 ]. E2 acyltransferases have an essential cofactor, lipoic acid, which is covalently bound via an amide linkage to a lysine group [ 2 ]. The lipoic acid cofactor is found in a variety of proteins that include, H-protein of the glycine cleavage system (GCS), mammalian and yeast pyruvate dehydrogenases and branched-chain 2-oxo acid dehydrogenase complex (BCOADC).

The lipoyl domains of 2-oxo acid dehydrogenase multienzyme complexes and the biotinyl domains of biotin-dependent enzymes have been solved, which revealed that they have homologous structures consisting of a flattened 8-stranded -barrel with the target lysine positioned in comparable beta-turns. Additional important residues for specificity have been identified, such as the conserved methionine flanking the target lysine that is essential for the recognition of the biotinyl domain by the biotinyl protein ligase [ 3 , 4 ].

1. The importance of methionine residues for the catalysis of the biotin enzyme, transcarboxylase. Analysis by site-directed mutagenesis. J. Biol. Chem. 267, 18407-12
2. Sequence similarities within the family of dihydrolipoamide acyltransferases and discovery of a previously unidentified fungal enzyme. Biochim. Biophys. Acta 1076, 225-32
3. Three-dimensional structure of the lipoyl domain from the dihydrolipoyl succinyltransferase component of the 2-oxoglutarate dehydrogenase multienzyme complex of Escherichia coli. J. Mol. Biol. 264, 179-90
4. Structure of the biotinyl domain of acetyl-coenzyme A carboxylase determined by MAD phasing. Structure 3, 1407-19