Catalysis of Orotidine 5'-Monophosphate: A Computational Study - Softcover

As a model for interactions present in the active site of orotidine-5'-monophosphate decarboxylase (ODCase), we investigated the effects of substrate destabilization by a nearby negative charge and stabilization of the carbanion intermediate, due to hydrogen bonds to the carbonyl groups (O-2 and O-4) of orotic acid and its decarboxylation product, using ab initio calculations. Results from these models were comparable with available data, suggesting that the magnitude of the decarboxylation rate enhancement depends on a combination of the charge distance and hydrogen bonding effects. We found that the dipole moment of the proton donor may also play a significant role, implying that the key to the rest of the catalysis lie within the specific interactions of the substrate and the surrounding residues.

Diana L. Shem received her B.S in Biochemistry and M.S. in Chemistry from San Francisco State University. She also received a M.A. in Education for Teaching of Chemistry from Stanford University in Palo Alto, California. Her other books include the instructional guide, "Mathematica Tutorial for Physical Chemistry," available for free online.