Src kinase conformational activation: thermodynamics, pathways, and mechanisms.

ABSTRACT: Tyrosine kinases of the Src-family are large allosteric enzymes that play a key role in cellular signaling. Conversion of the kinase from an inactive to an active state is accompanied by substantial structural changes. Here, we construct a coarse-grained model of the catalytic domain incorporating experimental structures for the two stable states, and simulate the dynamics of conformational transitions in kinase activation. We explore the transition energy landscapes by constructing a structural network among clusters of conformations from the simulations. From the structural network, two major ensembles of pathways for the activation are identified. In the first transition pathway, we find a coordinated switching mechanism of interactions among the alphaC helix, the activation-loop, and t

SUBMITTER: Yang S 

PROVIDER: S-EPMC2268010 | biostudies-literature | 2008 Mar

REPOSITORIES: biostudies-literature