Investigation of the enzymatic mechanism of the yeast chorismate mutase by docking a transition state analog

Shuo Liang Lin*, Dong Xu, Aijun Li, Maria Rosen, Haim J. Wolfson, Ruth Nussinov

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

The structure of the complex of the chorismate mutase from the yeast Saccharomyces cerevisiae with a transition state analog is constructed using a suite of docking tools. The construction finds the best location for the active site in the enzyme, and the best orientation of the analog compound in the active site. The resulting complex shows extensive salt links and hydrogen bonds between the enzyme and the compound, including those mediated by water molecules. A network of polar interactions between amino acid residues is found to solidify the active site of the enzyme. The enzymatic mechanism suggested for a bacterial chorismate mutase, that the active site is by design capable of selecting an active conformer of the substrate, and of stabilizing the transition state, is apparently intact in the yeast enzyme. No direct evidence is found to support an alternative mechanism which involves specific catalytic groups, although the possibility is not eliminated. This finding reinforces the notion of a function being evolutionarily conserved via a common mechanism, rather than via sequential or structural homology.

Original languageEnglish
Pages (from-to)838-845
Number of pages8
JournalJournal of Molecular Biology
Volume271
Issue number5
DOIs
StatePublished - 5 Sep 1997

Keywords

  • Chorismate
  • Docking
  • Modeling
  • Mutase
  • Structure

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