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
2020
FGF23 contains two distinct high-affinity binding sites enabling bivalent interactions with α-Klotho
Suzuki Y, Kuzina E, An SJ, Tome F, Mohanty J, Li W, Lee S, Liu Y, Lax I, Schlessinger J. FGF23 contains two distinct high-affinity binding sites enabling bivalent interactions with α-Klotho. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 31800-31807. PMID: 33257569, PMCID: PMC7749347, DOI: 10.1073/pnas.2018554117.Peer-Reviewed Original ResearchMeSH KeywordsBinding SitesCalcinosisCell MembraneFibroblast Growth Factor-23Fibroblast Growth FactorsGlucuronidaseHEK293 CellsHumansHyperostosis, Cortical, CongenitalHyperphosphatemiaImmunoglobulin Fc FragmentsKlotho ProteinsMutationOsteomalaciaProtein BindingProtein DomainsProtein MultimerizationRecombinant Fusion ProteinsRickets, HypophosphatemicConceptsFGF receptorsTotal internal reflection fluorescence microscopyChimeric receptor moleculesReflection fluorescence microscopyBinding sitesDisulfide bridge formationCritical metabolic processesMAPK responseCytoplasmic domainGrowth factor familyTerminal tailFactor familyKinase activationSimilar binding affinitiesExtracellular domainFGFR1 activationTandem repeatsMetabolic processesDisulfide bridgesCell surfaceDistinct ligandsCell membraneFluorescence microscopyDistinct high-affinity binding sitesPhosphate homeostasis
2013
Structural basis for KIT receptor tyrosine kinase inhibition by antibodies targeting the D4 membrane-proximal region
Reshetnyak AV, Nelson B, Shi X, Boggon TJ, Pavlenco A, Mandel-Bausch EM, Tome F, Suzuki Y, Sidhu SS, Lax I, Schlessinger J. Structural basis for KIT receptor tyrosine kinase inhibition by antibodies targeting the D4 membrane-proximal region. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 17832-17837. PMID: 24127596, PMCID: PMC3816449, DOI: 10.1073/pnas.1317118110.Peer-Reviewed Original ResearchConceptsKIT antibodyReceptor tyrosine kinase inhibitionGastrointestinal stromal tumorsAcute myeloid leukemiaDurable disease controlTyrosine kinase inhibitorsTyrosine kinase inhibitionSomatic oncogenic mutationsUnique therapeutic approachClinical progressionStromal tumorsMyeloid leukemiaTherapeutic approachesDramatic responseTreatment of KITDrug resistanceDisease controlIsolated antibodyKIT inhibitionKinase inhibitorsAntibodiesCancerCell proliferationOncogenic mutationsKinase inhibition
2006
Structural characterization of autoinhibited c-Met kinase produced by coexpression in bacteria with phosphatase
Wang W, Marimuthu A, Tsai J, Kumar A, Krupka H, Zhang C, Powell B, Suzuki Y, Nguyen H, Tabrizizad M, Luu C, West B. Structural characterization of autoinhibited c-Met kinase produced by coexpression in bacteria with phosphatase. Proceedings Of The National Academy Of Sciences Of The United States Of America 2006, 103: 3563-3568. PMID: 16537444, PMCID: PMC1450123, DOI: 10.1073/pnas.0600048103.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceBase SequenceCrystallography, X-RayCSK Tyrosine-Protein KinaseDNAEscherichia coliGene ExpressionGenetic VectorsModels, MolecularMutationNeoplasmsPhosphotransferasesProtein Structure, TertiaryProtein Tyrosine Phosphatase, Non-Receptor Type 1Protein Tyrosine PhosphatasesProtein-Tyrosine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-ablProto-Oncogene Proteins c-metRecombinant ProteinsSrc-Family KinasesConceptsC-Met kinaseKinase active siteC-Abl kinaseTyrosine phosphataseUnphosphorylated formSmall molecule compoundsKinase domainProtein kinaseC-SrcActive sitePhosphorylated formC-AblKinaseIntricate networkBicistronic vectorEscherichia coliLarge familyNormal regulationX-ray crystallographyEnzyme activityConformation stateSelective inhibitorDifferent conformation statesPhosphataseInhibitors
2005
Crystal Structures of Proto-oncogene Kinase Pim1: A Target of Aberrant Somatic Hypermutations in Diffuse Large Cell Lymphoma
Kumar A, Mandiyan V, Suzuki Y, Zhang C, Rice J, Tsai J, Artis D, Ibrahim P, Bremer R. Crystal Structures of Proto-oncogene Kinase Pim1: A Target of Aberrant Somatic Hypermutations in Diffuse Large Cell Lymphoma. Journal Of Molecular Biology 2005, 348: 183-193. PMID: 15808862, DOI: 10.1016/j.jmb.2005.02.039.Peer-Reviewed Original ResearchMeSH KeywordsAdenylyl ImidodiphosphateAmino Acid SequenceApoproteinsCrystallography, X-RayHumansLymphoma, Large B-Cell, DiffuseModels, MolecularMolecular Sequence DataMutationProtein BindingProtein ConformationProtein Serine-Threonine KinasesProto-Oncogene MasProto-Oncogene ProteinsProto-Oncogene Proteins c-pim-1Sequence AlignmentConceptsKinase activitySerine/threonine kinaseAberrant somatic hypermutationSomatic hypermutationKinase inhibitor scaffoldN-terminal lobePim1 mutantsTypical kinasesCo-crystal structureThreonine kinaseProtein kinaseBackbone hydrogen bondsKinase PIM1Apo formBiological functionsProline residuesPIM1 inhibitorsNovel chemical classUnique structural featuresLow molecular massInhibitor scaffoldsCell survivalMolecular massPosition 123PIM1