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Exploiting Enzyme Plasticity in Virtual Screening: High Efficiency Inhibitors of Glutamate Racemase.

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.

SUBMITTER: Whalen KL

PROVIDER: S-EPMC2903749 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

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Exploiting Enzyme Plasticity in Virtual Screening: High Efficiency Inhibitors of Glutamate Racemase.

Whalen Katie L KL Pankow Katherine L KL Blanke Steven R SR Spies M Ashley MA

ACS medicinal chemistry letters 20100401 1

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 sp ...[more]

PMID: 20634968

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