Targeting Dynamic ATP-Binding Site Features Allows Discrimination between Highly Homologous Protein Kinases.

ABSTRACT: ATP-competitive inhibitors that demonstrate exquisite selectivity for specific members of the human kinome have been developed. Despite this success, the identification of highly selective inhibitors is still very challenging, and it is often not possible to rationally engineer selectivity between the ATP-binding sites of kinases, especially among closely related family members. Src-family kinases (SFKs) are a highly homologous family of eight multidomain, nonreceptor tyrosine kinases that play general and specialized roles in numerous cellular processes. The high sequence and functional similarities between SFK members make it hard to rationalize how selectivity can be gained with inhibitors that target the ATP-binding site. Here, we describe the development of a series of inhibitors that

SUBMITTER: Chakraborty S 

PROVIDER: S-EPMC6642640 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature