Two-state dynamics of the SH3-SH2 tandem of Abl kinase and the allosteric role of the N-cap.

ABSTRACT: The regulation and localization of signaling enzymes is often mediated by accessory modular domains, which frequently function in tandems. The ability of these tandems to adopt multiple conformations is as important for proper regulation as the individual domain specificity. A paradigmatic example is Abl, a ubiquitous tyrosine kinase of significant pharmacological interest. SH3 and SH2 domains inhibit Abl by assembling onto the catalytic domain, allosterically clamping it in an inactive state. We investigate the dynamics of this SH3-SH2 tandem, using microsecond all-atom simulations and differential scanning calorimetry. Our results indicate that the Abl tandem is a two-state switch, alternating between the conformation observed in the structure of the autoinhibited enzyme and another conf

SUBMITTER: Corbi-Verge C 

PROVIDER: S-EPMC3767523 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature