2022
Biochemical and structural basis for differential inhibitor sensitivity of EGFR with distinct exon 19 mutations
van Alderwerelt van Rosenburgh I, Lu D, Grant M, Stayrook S, Phadke M, Walther Z, Goldberg S, Politi K, Lemmon M, Ashtekar K, Tsutsui Y. Biochemical and structural basis for differential inhibitor sensitivity of EGFR with distinct exon 19 mutations. Nature Communications 2022, 13: 6791. PMID: 36357385, PMCID: PMC9649653, DOI: 10.1038/s41467-022-34398-z.Peer-Reviewed Original Research
2021
Structural basis for ligand reception by anaplastic lymphoma kinase
Li T, Stayrook SE, Tsutsui Y, Zhang J, Wang Y, Li H, Proffitt A, Krimmer SG, Ahmed M, Belliveau O, Walker IX, Mudumbi KC, Suzuki Y, Lax I, Alvarado D, Lemmon MA, Schlessinger J, Klein DE. Structural basis for ligand reception by anaplastic lymphoma kinase. Nature 2021, 600: 148-152. PMID: 34819665, PMCID: PMC8639777, DOI: 10.1038/s41586-021-04141-7.Peer-Reviewed Original Research
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
2015
Conformation-Dependent Human p52Shc Phosphorylation by Human c‑Src
Tsutsui Y, Johnson J, Demeler B, Kinter M, Hays F. Conformation-Dependent Human p52Shc Phosphorylation by Human c‑Src. Biochemistry 2015, 54: 3469-3482. PMID: 25961473, DOI: 10.1021/acs.biochem.5b00122.Peer-Reviewed Original ResearchMeSH KeywordsCell MembraneCSK Tyrosine-Protein KinaseExtracellular Signal-Regulated MAP KinasesGRB2 Adaptor ProteinHumansMAP Kinase Signaling SystemPhosphatidylinositol PhosphatesPhosphorylationProtein StabilityProto-Oncogene Proteins p21(ras)Shc Signaling Adaptor ProteinsSrc Homology 2 Domain-Containing, Transforming Protein 1Src-Family KinasesConceptsHuman c-SrcMembrane-mimetic environmentsC-SrcPhosphorylation sitesAdaptor proteinGrb2 adaptor proteinPhosphorylation-dependent interactionPhosphorylation levelsRas/MAPKAmount of phosphorylationActive c-SrcCascade activationProtein phosphorylationMass spectrometry analysisComplex assemblyPhosphorylation statePhosphorylation statusP52ShcTyrosine residuesPhosphatidylinositol 4Tyrosine kinaseBiophysical characterizationInitial binding interactionGrb2Functional linkage
2014
Overproduction and biophysical characterization of human HSP70 proteins
Boswell-Casteel R, Johnson J, Duggan K, Tsutsui Y, Hays F. Overproduction and biophysical characterization of human HSP70 proteins. Protein Expression And Purification 2014, 106: 57-65. PMID: 25266791, PMCID: PMC4248018, DOI: 10.1016/j.pep.2014.09.013.Peer-Reviewed Original ResearchConceptsHuman HSP70 proteinHeat shock proteinsResponse pathwaysHSP70 proteinBiophysical characterizationFacilitate protein foldingVital cellular functionsInitial biophysical characterizationProtein-protein interactionsFuture biochemical studiesHeterologous overexpressionHSP functionCellular functionsProtein functionProtein foldingHSP70 familyFunctional characterizationConformational rearrangementsShock proteinsChemical stressorsHuman Hsp70HSP proteinsDownstream investigationsBiochemical studiesEscherichia coli
2012
Folding mechanism of the metastable serpin α1-antitrypsin
Tsutsui Y, Dela Cruz R, Wintrode P. Folding mechanism of the metastable serpin α1-antitrypsin. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 4467-4472. PMID: 22392975, PMCID: PMC3311335, DOI: 10.1073/pnas.1109125109.Peer-Reviewed Original Research
2011
Chapter Fifteen Probing Serpin Conformational Change Using Mass Spectrometry and Related Methods
Tsutsui Y, Sarkar A, Wintrode P. Chapter Fifteen Probing Serpin Conformational Change Using Mass Spectrometry and Related Methods. Methods In Enzymology 2011, 501: 325-350. PMID: 22078541, PMCID: PMC3679668, DOI: 10.1016/b978-0-12-385950-1.00015-8.Peer-Reviewed Original ResearchConceptsStructural mass spectrometry techniquesHydrogen/deuterium exchangeMass spectrometry techniquesDeuterium exchangeIon mobility mass spectrometrySpectrometry techniquesMass spectrometryMobility mass spectrometrySerpin polymersConformational flexibilitySerpin functionSerpin polymerizationChemical footprintingConformational changesThermodynamic metastabilitySpectrometryChapter FifteenSerpinsStructural distributionPolymerizationPolymersStabilityMisfoldingInhibitory mechanismFootprinting
2008
The Structural Basis of Serpin Polymerization Studied by Hydrogen/Deuterium Exchange and Mass Spectrometry*
Tsutsui Y, Kuri B, Sengupta T, Wintrode P. The Structural Basis of Serpin Polymerization Studied by Hydrogen/Deuterium Exchange and Mass Spectrometry*. Journal Of Biological Chemistry 2008, 283: 30804-30811. PMID: 18794298, PMCID: PMC2576545, DOI: 10.1074/jbc.m804048200.Peer-Reviewed Original Research