Acyl-CoA Carboxylases: Domains and Their Organization

We have gathered all amino acid sequences and three-dimensional structures available digitally of the multi-domain carbon-carbon bond-forming ligases (EC 6.4.1.–). EC 6.4.1.1 (pyruvate carboxylase), EC 6.4.1.6 (acetone carboxylase, of which no known amino acid sequences exist with evidence at protein level digitally), and EC 6.4.1.7 (2-oxoglutarate carboxylase) are fundamentally different from the acyl-CoA carboxylases (ACCs, EC 6.4.1.2 to EC 6.4.1.5) in not being active on substrates containing thioester groups linked to CoA. We are incorporating ACCs, which are important components of the fatty acid synthesis cycle, into the ThYme (Thioester-active enzYme) database. This will aid researchers worldwide who investigate these enzymes. We have found that all of these ligases share very similar biotin carboxylase and biotin carboxylase carrier protein domains. However, their carboxyl transferase domains (CTs) and the order in which their domains are located in the polypeptide chain, or even whether they form one chain, differ. For instance, there are two different CT domains, one found in EC 6.4.1.1 and EC 6.4.1.7, and the other found in EC 6.4.1.2 through 6.4.1.5. The second kind of CT domain exists in two different forms, CT-alpha and CT-Beta. The combination of these two forms or the absence of CT-alpha defines the CT domains in the ACCs.