Flooding enzymes: quantifying the contributions of interstitial water and cavity shape to ligand binding using extended linear response free energy calculations.

ABSTRACT: Glutamate racemase (GR) is a cofactor independent amino acid racemase that has recently garnered increasing attention as an antimicrobial drug target. There are numerous high resolution crystal structures of GR, yet these are invariably bound to either D-glutamate or very weakly bound oxygen-based salts. Recent in silico screens have identified a number of new competitive inhibitor scaffolds, which are not based on D-Glu, but exploit many of the same hydrogen bond donor positions. In silico studies on 1-H-benzimidazole-2-sulfonic acid (BISA) show that the sulfonic acid points to the back of the GR active site, in the most buried region, analogous to the C2-carboxylate binding position in the GR-d-glutamate complex. Furthermore, BISA has been shown to be the strongest nonamino acid competit

SUBMITTER: Whalen KL 

PROVIDER: S-EPMC3782002 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature