Catalytic mechanism of Escherichia coli isopentenyl diphosphate isomerase involves Cys-67, Glu-116, and Tyr-104 as suggested by crystal structures of complexes with transition state analogues and irreversible inhibitors

J. Wouters, Y. Oudjama, Sam J. Barkley, C. Tricot, V. Stalon, L. Droogmans, C. Dale Poulter

Research output: Contribution to journalArticle

Abstract

Isopentenyl diphosphate (IPP):dimethylallyl diphosphate (DMAPP) isomerase is a key enzyme in the biosynthesis of isoprenoids. The reaction involves protonation and deprotonation of the isoprenoid unit and proceeds through a carbocationic transition state. Analysis of the crystal structures (2 Å) of complexes of Escherichia coli IPP·DMAPPs isomerase with a transition state analogue (N,N-dimethyl-2-amino-1-ethyl diphosphate) and a covalently attached irreversible inhibitor (3,4-epoxy-3-methyl-1-butyl diphosphate) indicates that Glu-116, Tyr-104, and Cys-67 are involved in the antarafacial addition/ elimination of protons during isomerization. This work provides a new perspective about the mechanism of the reaction.

Original languageEnglish
Pages (from-to)11903-11908
Number of pages6
JournalJournal of Biological Chemistry
Volume278
Issue number14
DOIs
Publication statusPublished - 4 Apr 2003

Keywords

  • Biosynthesis
  • Ctalysis
  • Crystal structure
  • Escherichia coli
  • Isomerization

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