cAMP-DEPENDENT PROTEIN KINASE CONFORMATIONAL CHANGES INDUCED BY STAUROSPORINE AND OTHER INHIBITORS

D. Bossemeyer, A. Girod, V. Kinzel, R. Engh, R. Huber, L. Prade

Max-Planck-Institut fuer Biochemie, Am Klopferspitz 18a, 82152 Martinsried bei Muenchen, Germany,
E-mail: engh@biochem.mpg.de

Staurosporine and isoquinoline sulfonamide inhibitors bind to the cAMP- dependent protein kinase with several kinds of apparent induced fit rearrangements, including side chain rotamer adjustments, loop translations, and general lobe or subdomain rotations. A detailed understanding of these rearrangements requires distinguishing between true induced fit and effects of the crystal lattice. An understanding of the energetics of such adjustments also among other kinases is a prerequisite for effective modelling of new therapeutic kinase inhibitors with desired selectivity profiles.