BIOL 190 |
| Orotidine 5'-monophosphate decarboxylase (OMPDC) is a highly efficient catalyst of the chemically difficult decarboxylation of orotidine 5'-monophosphate (OMP) to give uridine 5'-monophosphate (UMP). We showed previously that binding of exogenous phosphite dianion to OMPDC results in an 80,000-fold increase in kcat/Km for decarboxylation of the truncated substrate 1-(ß-D-erythrofuranosyl)orotic acid (EO) that lacks a 5'-phosphodianion group. We have now examined the activation of OMPDC towards decarboxylation of the truncated substrates EO and orotidine by a range of inorganic oxydianions of varying size and oxygen basicity. We find that, like phosphite dianion, sulfite dianion is a highly a potent activator of OMPDC. The binding of this phosphodianion analog to OMPDC (Kd = 30 mM) results in a 40,000-fold increase in kcat/Km for decarboxylation of EO, which corresponds to a total intrinsic binding energy of sulfite dianion in the transition state of 8.4 kcal/mol. The data provide insight into the ability of the binding pocket of OMPDC to accommodate substrates and inorganic oxydianions of varying size and/or basicity.
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Enzymes
4:30 PM-6:30 PM, Wednesday, 13 September 2006 Moscone Center -- Hall D, Poster
Sci-Mix
Division of Biological Chemistry |
