Highly selective inhibition of myosin motors provides the basis of potential therapeutic application

• DOI: 10.1073/pnas.1609342113
• Publication Date: 2016-11-05T02:59:41Z
• Authors: Serena Sirigu; James J. Hartman; Vicente José Plan...; Virginie Ropars; Sheila Clancy; Xi Wang; Grace Chuang; Xiangping Qian; Pu-Ping Lu; Edward Barrett; Karin Rudolph; Christopher Royer; Bradley P. Morgan; Enrico A. Stura; Fady I. Malik; Anne M. Houdusse
• Keywords: Models, Molecular; drug design; [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM]; Muscle Relaxation; Myosin; Drug Evaluation, Preclinical; myosin; Crystallography, X-Ray; Drug design; Small Molecule Libraries; 03 medical and health sciences; Dogs; Models; Animals; Humans; Actin; Specific allosteric drugs; 0303 health sciences; Crystallography; Molecular Motor; Molecular; Muscle, Smooth; Smooth Muscle Myosins; Preclinical; Actins; Rats; molecular motor; specific allosteric drugs; [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology; X-Ray; Drug Evaluation; Muscle; Smooth; actin; Allosteric Site; Protein Binding

Significance Defects in myosin function are linked to a number of widespread and debilitating diseases, including asthma, chronic obstructive pulmonary disease, hypertrophic cardiomyopathy. We report here the discovery an allosteric site that modulates motor with high specificity opens path toward new therapeutic solutions. Identification specific antimyosin drugs significantly alter motor’s is imperative first step development targeted effective treatments for such diseases. Highly against different members superfamily would also provide exquisite tools investigate cells their functional role. Additionally, detailed, high-resolution studies interaction targets insights into molecular mechanism function.