Crystallographic snapshots of oxalyl-CoA decarboxylase give insights into catalysis by nonoxidative ThDP-dependent decarboxylases

Structure. 2007 Jul;15(7):853-61. doi: 10.1016/j.str.2007.06.001.


Despite more than five decades of extensive studies of thiamin diphosphate (ThDP) enzymes, there remain many uncertainties as to how these enzymes achieve their rate enhancements. Here, we present a clear picture of catalysis for the simple nonoxidative decarboxylase, oxalyl-coenzyme A (CoA) decarboxylase, based on crystallographic snapshots along the catalytic cycle and kinetic data on active site mutants. First, we provide crystallographic evidence that, upon binding of oxalyl-CoA, the C-terminal 13 residues fold over the substrate, aligning the substrate alpha-carbon for attack by the ThDP-C2 atom. The second structure presented shows a covalent reaction intermediate after decarboxylation, interpreted as being nonplanar. Finally, the structure of a product complex is presented. In accordance with mutagenesis data, no side chains of the enzyme are implied to directly participate in proton transfer except the glutamic acid (Glu-56), which promotes formation of the 1',4'-iminopyrimidine tautomer of ThDP needed for activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyl Coenzyme A / chemistry
  • Binding Sites
  • Carboxy-Lyases / chemistry*
  • Carboxy-Lyases / genetics
  • Catalysis
  • Coenzyme A / chemistry
  • Crystallography, X-Ray
  • Models, Molecular*
  • Mutation
  • Protein Folding
  • Recombinant Proteins / chemistry
  • Substrate Specificity
  • Thiamine Pyrophosphate / chemistry*


  • Acyl Coenzyme A
  • Recombinant Proteins
  • oxalyl-coenzyme A
  • formyl-coenzyme A
  • Carboxy-Lyases
  • oxalyl CoA decarboxylase
  • Thiamine Pyrophosphate
  • Coenzyme A

Associated data

  • PDB/2JI6
  • PDB/2JI7
  • PDB/2JI8
  • PDB/2JI9
  • PDB/2JIB