PROSITE documentation PDOC50980

Acetyl-coenzyme A carboxyltransferase domain profiles

Acetyl-coenzyme A carboxylase (EC 6.4.1.2) (ACC), a member of the biotin-dependent enzyme family, catalyses the formation of malonyl-coenzyme A (CoA) and regulates fatty acid biosynthesis and oxidation. Biotin-dependent carboxylase enzymes perform a two step reaction: enzyme-bound biotin is first carboxylated by bicarbonate and ATP and the carboxyl group temporarily bound to biotin is subsequently transferred to an acceptor substrate such as acetyl-CoA. The carboxyltransferase domain perform the second part of the reaction [1,2].

The N- and C-terminal regions of the carboxyltransferase domain share similar polypeptide backbone folds, with a central β-β-α superhelix (see <PDB:1OD2>) [3]. The CoA molecule is mostly associated with the N subdomain. In bacterial acetyl coenzyme A carboxylase the N and C subdomains are encoded by two different polypeptides.

The acetyl-coenzyme A carboxyltransferase domain is also found in the following enzymes:

• Methylcrotonyl-CoA carboxylase β chain, mitochondrial precursor (EC 6.4.1.4).
• Glutaconyl-CoA decarboxylase α subunit (EC 4.1.1.70).
• Propionyl-CoA carboxylase β chain (EC 6.4.1.3) (PCCase).

We developed two profiles for this domain, one that spans the N subdomain and also recognizes the bacterial ACC β-subunit, the other profile is directed against the C subdomain and recognizes also the α-subunit of bacterial ACC.