In Silico Screen and Structural Analysis Identifies Bacterial Kinase Inhibitors which Act with β-Lactams To Inhibit Mycobacterial Growth.

ABSTRACT: New tools and concepts are needed to combat antimicrobial resistance. Actinomycetes and firmicutes share several eukaryotic-like Ser/Thr kinases (eSTK) that offer antibiotic development opportunities, including PknB, an essential mycobacterial eSTK. Despite successful development of potent biochemical PknB inhibitors by many groups, clinically useful microbiologic activity has been elusive. Additionally, PknB kinetics are not fully described, nor are structures with specific inhibitors available to inform inhibitor design. We used computational modeling with available structural information to identify human kinase inhibitors predicted to bind PknB, and we selected hits based on drug-like characteristics intended to increase the likelihood of cell entry. The computational model suggested a

SUBMITTER: Wlodarchak N 

PROVIDER: S-EPMC6648700 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature