2016
Imatinib binding to human c-Src is coupled to inter-domain allostery and suggests a novel kinase inhibition strategy
Tsutsui Y, Deredge D, Wintrode P, Hays F. Imatinib binding to human c-Src is coupled to inter-domain allostery and suggests a novel kinase inhibition strategy. Scientific Reports 2016, 6: 30832. PMID: 27480221, PMCID: PMC4969603, DOI: 10.1038/srep30832.Peer-Reviewed Original ResearchConceptsHuman c-SrcC-SrcNon-receptor tyrosine kinase inhibitorsFunctional regulatory sitesC-Src SH3SH2 domainKinase domainHydrogen-deuterium exchangeKinase activationConformational dynamicsRegulatory sitesAllosteric siteMutation sitesKinase inhibitorsPatient tissuesInhibition strategiesAnti-neoplastic drugsPeptide ligandsDevelopment of TKICurrent study identifiesImatinib-resistant mutationsTyrosine kinase inhibitorsImatinib analogsMass spectrometryAllostery
2007
Cooperative Unfolding of a Metastable Serpin to a Molten Globule Suggests a Link Between Functional and Folding Energy Landscapes
Tsutsui Y, Wintrode P. Cooperative Unfolding of a Metastable Serpin to a Molten Globule Suggests a Link Between Functional and Folding Energy Landscapes. Journal Of Molecular Biology 2007, 371: 245-255. PMID: 17568610, DOI: 10.1016/j.jmb.2007.05.039.Peer-Reviewed Original ResearchConceptsMutagenesis studiesEquilibrium unfoldingMolten globuleCooperative structural unitDramatic conformational changeMultiple structural domainsNumerous mutagenesis studiesExchange mass spectrometryStable native stateNon-cooperative transitionPrevious mutagenesis studiesMolten globule formHydrogen-deuterium exchangeEquilibrium molten globuleFunctional intermediatesProtease-serpin complexesStructural domainsTarget proteasesConformational changesMetastable SerpinNative stateEquilibrium intermediatesCooperative unfoldingUnfolded stateGlobule form