Oxalyl-CoA decarboxylase
Template:Infobox enzyme The enzyme oxalyl-CoA decarboxylase (OXC) (Template:EnzExplorer), primarily produced by the gastrointestinal bacterium Oxalobacter formigenes, catalyzes the chemical reaction
- oxalyl-CoA formyl-CoA + CO2
OXC belongs to the family of lyases, specifically the carboxy-lyases (decarboxylases), which cleave carbon-carbon bonds. The systematic name of this enzyme class is oxalyl-CoA carboxy-lyase (formyl-CoA-forming). Other names in common use include oxalyl coenzyme A decarboxylase, and oxalyl-CoA carboxy-lyase. This enzyme participates in glyoxylate and dicarboxylate metabolism. It employs one cofactor, thiamin diphosphate (TPP), and plays a key role in catabolism of oxalate, a highly toxic compound that is a product of the oxidation of carbohydrates in many bacteria and plants.[1] Oxalyl-CoA decarboxylase is extremely important for the elimination of ingested oxalates found in human foodstuffs like coffee, tea, and chocolate,[2] and the ingestion of such foods in the absence of Oxalobacter formigenes in the gut can result in kidney disease or even death as a result of oxalate poisoning.[3]
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.[4] 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.[5] 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.[6] No FAD binding is observed in oxalyl-CoA decarboxylase,[7] 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.[8]> 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.[9][10]
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.[11] 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.[12]
Structure
Oxalyl-CoA decarboxylase is tetrameric, and each monomer consists of three α/β-type domains.[13] 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.[14][15]
See also
References
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