Structure of Full-Length Src Kinase and Its Key Phosphorylated States: Molecular Dynamics Study.

ABSTRACT: Src kinase is one of the key regulators of cellular metabolism and is dysregulated in numerous diseases, including cancer, neurodegenerative diseases, and particularly Alzheimer's disease. Despite its therapeutic importance, its full-length structure has never been obtained before, as it contains an intrinsically disordered regulatory region, SH4UD. The SH4UD region is crucial for Src activation, functional dimerization, and regulation by other kinases. In this study, we used the replica exchange molecular dynamics approach with a hybrid temperature and Hamiltonian tempering to obtain the conformational ensemble of full-length Src kinase in its non-phosphorylated state and in the presence of its two key regulatory phosphorylations: pY419 and pY530. The representative structures and simulat

SUBMITTER: Strelkova MA 

PROVIDER: S-EPMC11594451 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature