InterPro domain: IPR000891

Pyruvate carboxylase ( 6.4.1.1 ) (PC), a member of the biotin-dependent enzyme family, is involved in gluconeogenesis by mediating thecarboxylation of pyruvate to oxaloacetate. 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 pyruvate [ 1 ]. PC has three functional domains: a biotin carboxylase (BC) domain, a carboxyltransferase (CT) domain which perform the second part of the reaction and a biotinyl domain [ 2 , 3 ]. The pyruvate binding to the CT active site induces a conformational change stabilised by the interaction of conserved Asp and Tyr residues in this domain which leads to the formation of the biotin binding pocket and ensures the efficient coupling of BC and CT domain reactions [ 4 ]. The mechanism by which the carboxyl group is transferred from the carboxybiotin to the pyruvate is not well understood.

The pyruvate carboxyltransferase domain is also found in other pyruvate binding enzymes and acetyl-CoA dependent enzymes suggesting that this domain can be associated with different enzymatic activities.

This domain is found towards the N-terminal region of various aldolase enzymes. This N-terminal TIM barrel domain [ 5 ] interacts with the C-terminal domain. The C-terminal DmpG_comm domain ( IPR012425 ) is thought to promote heterodimerization with members of IPR003361 to form a bifunctional aldolase-dehydrogenase [ 6 ].

1. Chemical and catalytic mechanisms of carboxyl transfer reactions in biotin-dependent enzymes. Acc. Chem. Res. 35, 113-20
2. The structure and the mechanism of action of pyruvate carboxylase. Int. J. Biochem. Cell Biol. 27, 231-49
3. Structure, function and regulation of pyruvate carboxylase. Biochem. J. 340 ( Pt 1), 1-16
4. A substrate-induced biotin binding pocket in the carboxyltransferase domain of pyruvate carboxylase. J. Biol. Chem. 288, 19915-25
5. Crystal structure of a bifunctional aldolase-dehydrogenase: sequestering a reactive and volatile intermediate. Proc. Natl. Acad. Sci. U.S.A. 100, 6992-7