Biotin-dependent carboxylase enzymes perform a two step reaction. Enzyme-bound biotin is first carboxylated by bicarbonated and ATP and the carboxyl group temporarily bound to biotin is subsequently transferred to an acceptor substrate such as pyruvate or acetyl-CoA. The first step is mediated by the BC domain common to all biotin-dependent carboxylases [1]. The BC domain can be divided in three subdomains (N-terminal, central and C-terminal). The N-terminal region provides part of the active site; the central region corresponds to the ATP-grasp domain (see <PDOC50975>), which is common to many ATP-dependent enzymes involved in macromolecular synthesis [2]. The ATP-grasp module directly binds the ATP molecule. The C-terminal subdomain is involved in dimer formation.

Several structure of the BC domain have been solved (see for example <PDB:1ULZ>) [3,4]. The central module is splayed significantly away from the main body of the domain and is able to rotate of approximately 45 degree upon nucleotide binding thereby closing off the active site pocket [4].

Enzymes known to contain a BC domain are listed below:

• Pyruvate carboxylase (EC 6.4.1.1).
• Acetyl-/propionyl-coenzyme A carboxylase α chain (EC 6.4.1.3).
• Methylcrotonyl-CoA carboxylase α chain (EC 6.4.1.4).
• Urea amidolyase (EC 6.3.4.6).
• Acetyl-CoA carboxylase (EC 6.4.1.2).

The profile we developed covers the entire BC domain.