{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Chinthalapudi K"],"funding":["NIDCD NIH HHS","Medical Research Council","Wellcome Trust"],"pagination":["29700-8"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3191011"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["286(34)"],"pubmed_abstract":["Here, we report that the natural compound pentachloropseudilin (PClP) acts as a reversible and allosteric inhibitor of myosin ATPase and motor activity. IC(50) values are in the range from 1 to 5 ?m for mammalian class-1 myosins and greater than 90 ?m for class-2 and class-5 myosins, and no inhibition was observed with class-6 and class-7 myosins. We show that in mammalian cells, PClP selectively inhibits myosin-1c function. To elucidate the structural basis for PClP-induced allosteric coupling and isoform-specific differences in the inhibitory potency of the compound, we used a multifaceted approach combining direct functional, crystallographic, and in silico modeling studies. Our results indicate that allosteric inhibition by PClP is mediated by the combined effects of global changes in protein dynamics and direct communication between the catalytic and allosteric sites via a cascade of small conformational changes along a conserved communication pathway."],"journal":["The Journal of biological chemistry"],"pubmed_title":["Mechanism and specificity of pentachloropseudilin-mediated inhibition of myosin motor activity."],"pmcid":["PMC3191011"],"funding_grant_id":["DC008793","R01 DC008793","R55 DC008793","MC_U105184323","086743"],"pubmed_authors":["Fedorov R","Hartmann FK","Knolker HJ","Taft MH","Manstein DJ","Coluccio LM","Heissler SM","Brandstaetter H","Chinthalapudi K","Preller M","Gutzeit HO","Kendrick-Jones J","Tsiavaliaris G","Martin R","Buss F"],"additional_accession":[]},"is_claimable":false,"name":"Mechanism and specificity of pentachloropseudilin-mediated inhibition of myosin motor activity.","description":"Here, we report that the natural compound pentachloropseudilin (PClP) acts as a reversible and allosteric inhibitor of myosin ATPase and motor activity. IC(50) values are in the range from 1 to 5 ?m for mammalian class-1 myosins and greater than 90 ?m for class-2 and class-5 myosins, and no inhibition was observed with class-6 and class-7 myosins. We show that in mammalian cells, PClP selectively inhibits myosin-1c function. To elucidate the structural basis for PClP-induced allosteric coupling and isoform-specific differences in the inhibitory potency of the compound, we used a multifaceted approach combining direct functional, crystallographic, and in silico modeling studies. Our results indicate that allosteric inhibition by PClP is mediated by the combined effects of global changes in protein dynamics and direct communication between the catalytic and allosteric sites via a cascade of small conformational changes along a conserved communication pathway.","dates":{"release":"2011-01-01T00:00:00Z","publication":"2011 Aug","modification":"2021-02-20T03:43:00Z","creation":"2019-03-27T00:44:51Z"},"accession":"S-EPMC3191011","cross_references":{"pubmed":["21680745"],"doi":["10.1074/jbc.M111.239210"]}}