Structural contributions to multidrug recognition in the multidrug resistance (MDR) gene regulator, BmrR.

ABSTRACT: Current views of multidrug (MD) recognition focus on large drug-binding cavities with flexible elements. However, MD recognition in BmrR is supported by a small, rigid drug-binding pocket. Here, a detailed description of MD binding by the noncanonical BmrR protein is offered through the combined use of X-ray and solution studies. Low shape complementarity, suboptimal packing, and efficient burial of a diverse set of ligands is facilitated by an aromatic docking platform formed by a set of conformationally fixed aromatic residues, hydrophobic pincer pair that locks the different drug structures on the adaptable platform surface, and a trio of acidic residues that enables cation selectivity without much regard to ligand structure. Within the binding pocket is a set of BmrR-derived H-bonding

SUBMITTER: Bachas S 

PROVIDER: S-EPMC3131311 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature