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

ACS Medicinal Chemistry Letters
Katie L WhalenM Ashley Spies

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.

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Sep 15, 2011·Chemical Reviews·Paola ContiCarlo De Micheli
Aug 8, 2015·Journal of Chemical Information and Modeling·Fredrik SvenssonChristian Sköld
Sep 19, 2012·The Journal of Physical Chemistry. B·Edgar MixcohaAngels González-Lafont
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