Exploiting enzyme plasticity in virtual screening: High efficiency inhibitors of glutamate racemase

Katie L. Whalen, Katherine L. Pankow, Steven R. Blanke, M. Ashley Spies

Research output: Contribution to journalArticle

Abstract

Glutamate racemase is an attractive antimicrobial drug target. Virtual screening using a transition-state conformation of the enzyme resulted in the discovery of several μM competitive inhibitors, dissimilar from current amino acid-like inhibitors, providing novel scaffolds for drug discovery. The most effective of these competitive inhibitors possesses a very high ligand efficiency value of -0.6 kcal/mol/heavy atom, and is effective against three distinct glutamate racemases representing two species of Bacillus. The benefits of employing the transition-state conformation of the receptor in virtual screening are discussed.

Original languageEnglish (US)
Pages (from-to)9-13
Number of pages5
JournalACS Medicinal Chemistry Letters
Volume1
Issue number1
DOIs
StatePublished - Apr 8 2010

Keywords

  • Glutamate racemase
  • inhibitor
  • protein dynamics
  • virtual screening

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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