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 homeostasisSelective Janus Kinase 2 (JAK2) Pseudokinase Ligands with a Diaminotriazole Core
Liosi ME, Krimmer SG, Newton AS, Dawson T, Puleo DE, Cutrona KJ, Suzuki Y, Schlessinger J, Jorgensen WL. Selective Janus Kinase 2 (JAK2) Pseudokinase Ligands with a Diaminotriazole Core. Journal Of Medicinal Chemistry 2020, 63: 5324-5340. PMID: 32329617, PMCID: PMC7949251, DOI: 10.1021/acs.jmedchem.0c00192.Peer-Reviewed Original Research
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 123PIM1A family of phosphodiesterase inhibitors discovered by cocrystallography and scaffold-based drug design
Card GL, Blasdel L, England BP, Zhang C, Suzuki Y, Gillette S, Fong D, Ibrahim PN, Artis DR, Bollag G, Milburn MV, Kim SH, Schlessinger J, Zhang KY. A family of phosphodiesterase inhibitors discovered by cocrystallography and scaffold-based drug design. Nature Biotechnology 2005, 23: 201-207. PMID: 15685167, DOI: 10.1038/nbt1059.Peer-Reviewed Original ResearchConceptsDrug designX-ray crystallographyStructural analysisChemical synthesisDetailed structural analysisScaffold derivativesPyrazole derivativesChemical substitutionPotent PDE4 inhibitorsCarboxylic estersCellular processesDrug candidatesMolecular basisNew inhibitorsCyclic nucleotide phosphodiesterasesCocrystallographyLarge familyCompoundsNucleotide phosphodiesterasesDerivativesPhosphodiesterasesCrystallographyInhibitorsEfficient methodFamily