D
IPR000891

Pyruvate carboxyltransferase

InterPro entry
Short namePYR_CT
Overlapping
homologous
superfamilies
 
domain relationships

Description

Pyruvate carboxylase (
6.4.1.1
) (PC), a member of the biotin-dependent enzyme family, is involved in gluconeogenesis by mediating the carboxylation 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
[5]
. 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.

For examples, this domain is found in various synthase enzymes, including methylthioalkylmalate synthases involved in the conversion of 4-methylsulfanyl-2-oxobutanoate into 2-(2-methylsulfanyl)ethylmalate
[6]
.

This domain is found towards the N-terminal region of various aldolase enzymes. This N-terminal TIM barrel domain
[4]
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
[4]
.

References

1.Chemical and catalytic mechanisms of carboxyl transfer reactions in biotin-dependent enzymes. Attwood PV, Wallace JC. Acc. Chem. Res. 35, 113-20, (2002). View articlePMID: 11851389

2.The structure and the mechanism of action of pyruvate carboxylase. Attwood PV. Int. J. Biochem. Cell Biol. 27, 231-49, (1995). View articlePMID: 7780827

3.Structure, function and regulation of pyruvate carboxylase. Jitrapakdee S, Wallace JC. Biochem. J. 340 ( Pt 1), 1-16, (1999). View articlePMID: 10229653

4.Crystal structure of a bifunctional aldolase-dehydrogenase: sequestering a reactive and volatile intermediate. Manjasetty BA, Powlowski J, Vrielink A. Proc. Natl. Acad. Sci. U.S.A. 100, 6992-7, (2003). View articlePMID: 12764229

5.A substrate-induced biotin binding pocket in the carboxyltransferase domain of pyruvate carboxylase. Lietzan AD, St Maurice M. J. Biol. Chem. 288, 19915-25, (2013). PMID: 23698000

6.Characterization of unique EDTA-insensitive methylthioalkylmalate synthase from Eutrema japonicum and its potential application in synthetic biology. Medhanavyn D, Muranaka T, Yasumoto S. J Biosci Bioeng 138, 13-20, (2024). View articlePMID: 38614832

GO terms

biological process

  • None

cellular component

  • None

Cross References

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