TY - JOUR TI - Allosteric inhibition of kinesin-5 modulates its processive directional motility. AU - Kwok, Benjamin H. AU - Kapitein, Lukas C. AU - Kim, Jeffrey H. AU - Peterman, Erwin J. G. AU - Schmidt, Christoph F. AU - Kapoor, Tarun M. T2 - Nature chemical biology AB - Small-molecule inhibitors of kinesin-5 (refs. 1-3), a protein essential for eukaryotic cell division, represent alternatives to antimitotic agents that target tubulin. While tubulin is needed for multiple intracellular processes, the known functions of kinesin-5 are limited to dividing cells, making it likely that kinesin-5 inhibitors would have fewer side effects than do tubulin-targeting drugs. Kinesin-5 inhibitors, such as monastrol, act through poorly understood allosteric mechanisms, not competing with ATP binding. Moreover, the microscopic mechanism of full-length kinesin-5 motility is not known. Here we characterize the motile properties and allosteric inhibition of Eg5, a vertebrate kinesin-5, using a GFP fusion protein in single-molecule fluorescence assays. We find that Eg5 is a processive kinesin whose motility includes, in addition to ATP-dependent directional motion, a diffusive component not requiring ATP hydrolysis. Monastrol suppresses the directional processive motility of microtubule-bound Eg5. These data on Eg5's allosteric inhibition will impact these inhibitors' use as probes and development as chemotherapeutic agents. DA - 2006/09//undefined PY - 2006 DO - 10.1038/nchembio812 VL - 2 IS - 9 SP - 480 EP - 485 J2 - Nat Chem Biol LA - eng SN - 1552-4450 1552-4450 KW - Allosteric Regulation KW - Animals KW - Antimitotic Agents/pharmacology KW - Green Fluorescent Proteins/metabolism KW - Kinesin/*antagonists & inhibitors KW - Microscopy, Fluorescence KW - Microtubules/drug effects/*metabolism KW - Pyrimidines/pharmacology KW - Recombinant Fusion Proteins/*metabolism KW - Spindle Apparatus/drug effects/*metabolism KW - Thiones/pharmacology KW - Xenopus Proteins/*antagonists & inhibitors KW - Xenopus laevis ER -