The structural basis of blebbistatin inhibition and specificity for myosin II.
Molecular motors play a central role in cytoskeletal-mediated cellular processes and thus present an excellent target for cellular control by pharmacological agents. Yet very few such compounds have been found. We report here the structure of blebbistatin, which inhibits specific myosin isoforms, bound to the motor domain of Dictyostelium discoideum myosin II. This reveals the structural basis for its specificity and provides insight into the development of new agents.
Allingham
John S
JS
Department of Biochemistry, University of Wisconsin, 433 Babcock Drive, Madison, Wisconsin 53706, USA.
Smith
Robert
R
Rayment
Ivan
I
D000818:Animals; D001665:Binding Sites; D004023:Dictyostelium / Q000737:chemistry / Q000378:metabolism; D006576:Heterocyclic Compounds, 4 or More Rings / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D024462:Myosin Type II / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D013379:Substrate Specificity
D006576:Heterocyclic Compounds, 4 or More Rings; D020033:Protein Isoforms; C472645:blebbistatin; D024462:Myosin Type II