Oxalyl-CoA decarboxylase

Evolution

Oxalyl-CoA decarboxylase is hypothesized to be evolutionarily related to acetolactate synthase, a TPP-dependent enzyme responsible for the biosynthesis of branched chain amino acids in certain organisms. Sequence alignments between the two enzymes support this claim, as do the presence of vestigial FAD-binding pockets that play no role in either enzyme's catalytic activity. The binding of FAD at this site in acetolactate synthase and the binding of ADP at a cognate site in OXC are thought to play roles in the stabilization of the tertiary structures of the proteins. No FAD binding is observed in oxalyl-CoA decarboxylase, but an excess of coenzyme A in the crystal structure has led to the hypothesis that the binding site was co-opted during OXC evolution to bind the CoA moiety of its substrate. Despite their similarities, only oxalyl-CoA decarboxylase is necessary for the formation of ATP in Oxalobacter formigenes, and exogenous ADP has been demonstrated to increase the decarboxylase activity of OXC, but not acetolactate synthase.

Reaction mechanism

A key feature of the cofactor TPP is the relatively acidic proton bound to the carbon atom between the nitrogen and sulfur in the thiazole ring, which has a pKa near 10. This carbon center ionizes to form a carbanion, which adds to the carbonyl group of oxalyl-CoA. This addition is followed by the decarboxylation of oxalyl-CoA, and then the oxidation and removal of formyl-CoA to regenerate the carbanion form of TPP. While the reaction mechanism is shared with other TPP-dependent enzymes, the residues found in the active site of OXC are unique, which has raised questions about whether TDP must be deprotonated by a basic amino acid at a second site away from the carbanion-forming site to activate the cofactor.

Structure

Oxalyl-CoA decarboxylase is tetrameric, and each monomer consists of three α/β-type domains. The thiamine diphosphate-binding site rests on the subunit-subunit interface between two of the domains, which is commonly seen in its class of enzymes. Oxalyl-CoA decarboxylase is structurally homologous to acetolactate synthase found in plants and other microorganisms, but OXC binds ADP in a region that is similar to the FAD-binding site in acetolactate synthase.

References

References

1. (July 1990). "Purification and characterization of formyl-coenzyme A transferase from Oxalobacter formigenes". Journal of Bacteriology.
2. (2007). "Tea and coffee as the main sources of oxalate in diets of patients with kidney oxalate stones". Roczniki Panstwowego Zakladu Higieny.
3. (August 2010). "Oxalate-degrading activity in Bifidobacterium animalis subsp. lactis: impact of acidic conditions on the transcriptional levels of the oxalyl coenzyme A (CoA) decarboxylase and formyl-CoA transferase genes". Applied and Environmental Microbiology.
4. (February 1986). "Acetohydroxy acid synthase I, a required enzyme for isoleucine and valine biosynthesis in Escherichia coli K-12 during growth on acetate as the sole carbon source". Journal of Bacteriology.
5. (June 1998). "Biosynthesis of 2-aceto-2-hydroxy acids: acetolactate synthases and acetohydroxyacid synthases". Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology.
6. (November 1989). "Flavin adenine dinucleotide causes oligomerization of acetohydroxyacid synthase from Black Mexican Sweet corn cells.". FEBS Letters.
7. (January 2005). "The enzymes of oxalate metabolism: unexpected structures and mechanisms". Archives of Biochemistry and Biophysics.
8. (July 2007). "Crystallographic snapshots of oxalyl-CoA decarboxylase give insights into catalysis by nonoxidative ThDP-dependent decarboxylases". Structure.
9. (August 2000). "Regulation by external pH and stationary growth phase of the acetolactate synthase from Synechocystis PCC6803". Molecular Microbiology.
10. (January 1975). "Regulation of acetohydroxy acid synthase in streptomycin-dependent Escherichia coli". Journal of Bacteriology.
11. "Biochemistry". W.H. Freeman and Company.
12. (December 2005). "Structural basis for activation of the thiamin diphosphate-dependent enzyme oxalyl-CoA decarboxylase by adenosine diphosphate". The Journal of Biological Chemistry.
13. (June 2010). "New insights into structure-function relationships of oxalyl CoA decarboxylase from Escherichia coli". The FEBS Journal.
14. (2000). "Acetohydroxyacid Synthase". Journal of Biochemistry and Molecular Biology.
15. (March 2006). "Transcriptional and functional analysis of oxalyl-coenzyme A (CoA) decarboxylase and formyl-CoA transferase genes from Lactobacillus acidophilus". Applied and Environmental Microbiology.