The binding interactions between enzyme catalysts and stable, nonreacting, fragments of bound substrate were assumed to serve the exclusive function of anchoring substrates to their catalysts, until our demonstration that interactions between the protein and substrate phosphodianion strongly activate enzymes for catalysis of proton, hydride and phosphoryl transfer, and decarboxylation reactions. Interactions between orotidine 5'-monophosphate decarboxylase (OMPDC) and the C-2 and C-3 hydroxyls at the ribofuranosyl ring activate this enzyme for catalysis of decarboxylation of a truncated 5-fluoroorotate substrate [2]. We now examine the contribution of specific interactions between Asp37 and Thr100' from OMPDC and bound substrates or activators to the enzymatic rate acceleration. We report the effects of several mutations of these side chains on the kinetic parameters for the following OMPDC-catalyzed decarboxylation reactions: (1) Decarboxylation of the whole substrates orotidine 5'-monophosphate and 5-fluoroorotidine 5'-monophosphate. (2) Decarboxylation of two phosphodianion truncated substrates and of the activation of decarboxylation by phosphite dianion. (3) Decarboxylation of 5-fluoroorotate activated by phosphite dianion and by 3- and 4-carbon sugar phosphates.<br/><br/>

Activation of orotidine 5’-monophosphate decarboxylase by interactions between substrate or activator ribosyl hydroxyls and the side chains from Asp 37 and T100'

2019 Fall National Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.