Structures of staurosporine bound to CDK2 and cAPK--new tools for structure-based design of protein kinase inhibitors.
Protein kinases are involved in a wide variety of signal transduction processes; their deregulation has been implicated in a number of human diseases, including cancer and disorders of the immune system. The recently determined structures of two protein kinases, cAPK and CDK2, in complex with an inhibitor, staurosporine, provide a detailed account of inhibitor-kinase interactions and inhibitor selectivity.
Toledo
L M
LM
Kinetix Pharmaceuticals, Inc., Medford, MA 02155, USA.
Lydon
N B
NB
D001665:Binding Sites; D042846:CDC2-CDC28 Kinases; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis*; D008958:Models, Molecular; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D019311:Staurosporine / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D017346:Protein Serine-Threonine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D042846:CDC2-CDC28 Kinases; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; D019311:Staurosporine