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 language | English (US) |
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Pages (from-to) | 9-13 |
Number of pages | 5 |
Journal | ACS Medicinal Chemistry Letters |
Volume | 1 |
Issue number | 1 |
DOIs | |
State | Published - Apr 8 2010 |
Keywords
- Glutamate racemase
- inhibitor
- protein dynamics
- virtual screening
ASJC Scopus subject areas
- Biochemistry
- Drug Discovery
- Organic Chemistry