Report

A Proficient Enzyme Revisited: The Predicted Mechanism for Orotidine Monophosphate Decarboxylase

Science  09 May 1997:
Vol. 276, Issue 5314, pp. 942-945
DOI: 10.1126/science.276.5314.942

You are currently viewing the abstract.

View Full Text

Via your Institution

Log in through your institution

Log in through your institution


Abstract

A mechanism is proposed to explain the activity of orotidine 5′-monophosphate decarboxylase (ODCase). This enzyme is the one of the most proficient known, with a catalytic proficiency (k cat/K m)/k non= 1023 M−1. Quantum mechanical calculations predict a mechanism involving a stabilized carbene intermediate, which represents a previously unrecognized mode of enzymatic activity for ODCase. The proposed mechanism involves proton transfer from a weak acid (pK a = 7, where K ais the acid constant) concerted with decarboxylation, in a nonpolar enzyme environment. Such a mechanism makes possible different approaches to the design of ODCase inhibitors. Furthermore, the prediction that general acid catalysis may only be effective in low dielectric media is of general significance for understanding the activity of many enzymes.

View Full Text

Cited By...