The structural basis for the remarkable catalytic proficiency of orotidine 5'-monophosphate decarboxylase.
The three-dimensional structures of orotidine 5'-monophosphate decarboxylases from four different organisms have been determined by X-ray crystallography. The structures reveal an active site in which the pyrimidine base and phosphate groups are rigidly held in place. Surprisingly, both pyrimidine carbonyl groups are hydrogen bonded to amide groups, rather than to strong active site acids, as was previously predicted. The positioning of a conserved aspartate sidechain close to the substrate carboxylate and a conserved lysine ammonium group close to the C6 of the pyrimidine suggests a novel mechanism to explain the extreme catalytic proficiency of this enzyme.
Begley
T P
TP
Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA. tpb2@cornell.edu
Appleby
T C
TC
Ealick
S E
SE
D000595:Amino Acid Sequence; D002384:Catalysis; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009964:Orotidine-5'-Phosphate Decarboxylase / Q000737:chemistry / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
D009964:Orotidine-5'-Phosphate Decarboxylase