Rational Design of Selective Adenine-Based Scaffolds for Inactivation of Bacterial Histidine Kinases.

ABSTRACT: Bacterial histidine kinases (HKs) are quintessential regulatory enzymes found ubiquitously in bacteria. Apart from their regulatory roles, they are also involved in the production of virulence factors and conferring resistance to various antibiotics in pathogenic microbes. We have previously reported compounds that inhibit multiple HKs by targeting the conserved catalytic and ATP-binding (CA) domain. Herein, we conduct a detailed structure-activity relationship assessment of adenine-based inhibitors using biochemical and docking methods. These studies have resulted in several observations. First, interaction of an inhibitor's amine group with the conserved active-site Asp is essential for activity and likely dictates its orientation in the binding pocket. Second, a N-NH-N triad in the inhi

SUBMITTER: Goswami M 

PROVIDER: S-EPMC5743200 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature