Modest catalysis of the decarboxylation of orotate by hydrogen bonding: a theoretical model for orotidine- 5' -monophosphate decarboxylase.
As a model for interactions present in the active site of orotidine-5'-monophosphate decarboxylase (ODCase), the effect of hydrogen bonds to the carbonyl groups (O-2 and O-4) of orotic acid and its decarboxylation product was probed with ab initio calculations. We have found that the transition state/carbanion intermediate is a better proton receptor and therefore, the hydrogen bonds can be a modest source of catalysis. Comparison of the calculated data with results from site-directed mutagenesis provides some insights into the polarity of the active site.
Shem
Diana L
DL
Department of Chemistry and Biochemistry, San Francisco State University, San Francisco, CA 94132, USA.
Gronert
Scott
S
Wu
Weiming
W
D002384:Catalysis; D003653:Decarboxylation; D005561:Formates / Q000494:pharmacology; D006860:Hydrogen Bonding; D015394:Molecular Structure; D009963:Orotic Acid / Q000378:metabolism*; D009964:Orotidine-5'-Phosphate Decarboxylase / Q000737:chemistry / Q000378:metabolism*
D005561:Formates; C030544:formic acid; D009963:Orotic Acid; D009964:Orotidine-5'-Phosphate Decarboxylase