The Activation of c-Src Tyrosine Kinase: Conformational Transition Pathway and Free Energy Landscape.

ABSTRACT: Tyrosine kinases are important cellular signaling allosteric enzymes that regulate cell growth, proliferation, metabolism, differentiation, and migration. Their activity must be tightly controlled, and malfunction can lead to a variety of diseases, particularly cancer. The nonreceptor tyrosine kinase c-Src, a prototypical model system and a representative member of the Src-family, functions as complex multidomain allosteric molecular switches comprising SH2 and SH3 domains modulating the activity of the catalytic domain. The broad picture of self-inhibition of c-Src via the SH2 and SH3 regulatory domains is well characterized from a structural point of view, but a detailed molecular mechanism understanding is nonetheless still lacking. Here, we use advanced computational methods based on a

SUBMITTER: Fajer M 

PROVIDER: S-EPMC5398919 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature