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