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
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
2004
A Glutamine Switch Mechanism for Nucleotide Selectivity by Phosphodiesterases
Zhang KY, Card GL, Suzuki Y, Artis DR, Fong D, Gillette S, Hsieh D, Neiman J, West BL, Zhang C, Milburn MV, Kim SH, Schlessinger J, Bollag G. A Glutamine Switch Mechanism for Nucleotide Selectivity by Phosphodiesterases. Molecular Cell 2004, 15: 279-286. PMID: 15260978, DOI: 10.1016/j.molcel.2004.07.005.Peer-Reviewed Original ResearchMeSH Keywords3',5'-Cyclic-AMP Phosphodiesterases3',5'-Cyclic-GMP PhosphodiesterasesCatalytic DomainCrystallography, X-RayCyclic AMPCyclic GMPCyclic Nucleotide Phosphodiesterases, Type 3Cyclic Nucleotide Phosphodiesterases, Type 4Cyclic Nucleotide Phosphodiesterases, Type 5GlutamineHumansModels, MolecularProtein ConformationConceptsNucleotide selectivityKey specificity determinantKey histidine residuesFamily of enzymesHigh-resolution co-crystal structuresCo-crystal structureNew PDE inhibitorsGlutamine switchInvariant glutamineSpecificity determinantsTypes of phosphodiesterasesGlutamine functionsGlutamine residuesHistidine residuesSwitch mechanismStructural understandingPhosphodiesterasesCyclic nucleotidesResiduesCritical rolePurine moietyCGMPCAMPPDE inhibitorsNucleotides