Identification of an auxiliary druggable pocket in the DNA gyrase ATPase domain using fragment probes.

ABSTRACT: Discovery of new drug binding sites on well-established targets is of great interest as it facilitates the design of new mechanistic inhibitors to overcome the acquired drug resistance. Small chemical fragments can easily enter and bind to the cavities on the protein surface. Thus, they can be used to probe new druggable pockets in proteins. DNA gyrase plays indispensable roles in DNA replication, and both its GyrA and GyrB subunits are clinically validated antibacterial targets. New mechanistic GyrB inhibitors are urgently desired since the withdrawal of novobiocin from the market by the FDA due to its reduced efficiency and other reasons. Here, a fragment library was screened against the E. coli GyrB ATPase domain by combining affinity- and bioactivity-based approaches. The follow

SUBMITTER: Huang X 

PROVIDER: S-EPMC6194491 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature