2024
Structural Basis for p19 Targeting by Anti–IL-23 Biologics: Correlations with Short- and Long-Term Efficacy in Psoriasis
Daniele S, Eldirany S, Damiani G, Ho M, Bunick C. Structural Basis for p19 Targeting by Anti–IL-23 Biologics: Correlations with Short- and Long-Term Efficacy in Psoriasis. JID Innovations 2024, 4: 100261. PMID: 38445231, PMCID: PMC10914523, DOI: 10.1016/j.xjidi.2024.100261.Peer-Reviewed Original ResearchIL-23Clinical efficacyIL-23 inhibitors risankizumabSurface areaLong-term clinical efficacyMolecular propertiesIL-23 inhibitorsSolvent accessible surface areaHydrogen-deuterium exchangeIL-23 p19 subunitAccessible surface areaAssociated with short-Clinical efficacy scorePlaque psoriasisClinical responseP19 subunitCrystallographic experimentsPsoriasis pathogenesisReceptor epitopesInhibitor epitopesPsoriasisLinear regression analysisEfficacyTherapeutic classesBinding affinity
2022
Case Study: Metabolism and Reactions of Alkylating Agents in Cancer Therapy
NASSAR A, WISNEWSKI A, KING I. Case Study: Metabolism and Reactions of Alkylating Agents in Cancer Therapy. 2022, 893-922. DOI: 10.1002/9781119851042.ch26.Peer-Reviewed Original ResearchNuclear magnetic resonance spectroscopyCollision-induced dissociationFourier transform ion cyclotron resonance mass spectrometerIon cyclotron resonance mass spectrometerAccurate mass measurementsMass spectrometry studiesHydrogen-deuterium exchangeMagnetic resonance spectroscopyMass spectral rearrangementsExact massSpectrometry studiesEnzyme catalysisReactive intermediatesMass spectrometerDecomposition productsResonance spectroscopyConjugation reactionsElemental compositionPossibility of rearrangementMass measurementsSpectral rearrangementsReactionDissociationRadioactive componentsLoss of nitrogen
2017
Conformational dynamics of a neurotransmitter:sodium symporter in a lipid bilayer
Adhikary S, Deredge DJ, Nagarajan A, Forrest LR, Wintrode PL, Singh SK. Conformational dynamics of a neurotransmitter:sodium symporter in a lipid bilayer. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: e1786-e1795. PMID: 28223522, PMCID: PMC5347597, DOI: 10.1073/pnas.1613293114.Peer-Reviewed Original ResearchConceptsSodium symportersMembrane proteinsMammalian membrane proteinsConformational mechanismIntegral membrane proteinsPhospholipid bilayer nanodiscsSolution spectroscopyDetergent-solubilized stateExtracellular loop 2Site-specific labelingSmall molecule neurotransmittersBilayer nanodiscsHydrogen-deuterium exchangeX-ray crystallographyCysteine accessibilityConformational dynamicsMembrane mimicsMolecular dynamics simulationsLoop 2Endogenous cysteineHelices 1ALeuTLipid bilayersProteinSymporter
2016
Structural Basis for the Procofactor to Cofactor Transition in Human Factor V
Kumar S, Deng W, Stayrook S, Li R, Camire R, Krishnaswamy S. Structural Basis for the Procofactor to Cofactor Transition in Human Factor V. Blood 2016, 128: 253. DOI: 10.1182/blood.v128.22.253.253.Peer-Reviewed Original ResearchBasic regionB domainC-terminusLong standing puzzleBR bindingCrystal structureDocking studiesBr fragmentsHuman factor VCentral B domainA2 domainAmide proton exchange ratesPhosphatidylserine-containing membranesAr2Hydrogen-deuterium exchangeA1-A2-B-A3-C1-C2Adjacent regionsAmide proton exchangeComputational docking studiesProton exchange ratesDomain organizationAcid sequenceProteolytic excisionCofactor formationPrimary structureImatinib 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 spectrometryAllosteryBiotransformation and Rearrangement of Laromustine
Nassar AE, Wisnewski AV, King I. Biotransformation and Rearrangement of Laromustine. Drug Metabolism And Disposition 2016, 44: 1349-1363. PMID: 27278961, DOI: 10.1124/dmd.116.069823.Peer-Reviewed Original ResearchConceptsNuclear magnetic resonance spectroscopyCollision-induced dissociationFourier transform ion cyclotron resonance mass spectrometerIon cyclotron resonance mass spectrometerAccurate mass measurementsMass spectrometry studiesHydrogen-deuterium exchangeMagnetic resonance spectroscopyMass spectral rearrangementsExact massSpectrometry studiesEnzyme catalysisReactive intermediatesMass spectrometerDecomposition productsResonance spectroscopyConjugation reactionsElemental compositionPossibility of rearrangementMass measurementsSpectral rearrangementsDissociationRadioactive componentsLoss of nitrogenMetabolite products
2007
Cooperative Unfolding of a Metastable Serpin to a Molten Globule Suggests a Link Between Functional and Folding Energy Landscapes
Tsutsui Y, Wintrode P. Cooperative Unfolding of a Metastable Serpin to a Molten Globule Suggests a Link Between Functional and Folding Energy Landscapes. Journal Of Molecular Biology 2007, 371: 245-255. PMID: 17568610, DOI: 10.1016/j.jmb.2007.05.039.Peer-Reviewed Original ResearchConceptsMutagenesis studiesEquilibrium unfoldingMolten globuleCooperative structural unitDramatic conformational changeMultiple structural domainsNumerous mutagenesis studiesExchange mass spectrometryStable native stateNon-cooperative transitionPrevious mutagenesis studiesMolten globule formHydrogen-deuterium exchangeEquilibrium molten globuleFunctional intermediatesProtease-serpin complexesStructural domainsTarget proteasesConformational changesMetastable SerpinNative stateEquilibrium intermediatesCooperative unfoldingUnfolded stateGlobule form
2006
Interaction of packaging motor with the polymerase complex of dsRNA bacteriophage
Lísal J, Kainov DE, Lam TT, Emmett MR, Wei H, Gottlieb P, Marshall AG, Tuma R. Interaction of packaging motor with the polymerase complex of dsRNA bacteriophage. Virology 2006, 351: 73-79. PMID: 16643976, DOI: 10.1016/j.virol.2006.03.025.Peer-Reviewed Original ResearchConceptsC-terminal faceP4 hexamersDsRNA bacteriophagesPackaging motorPolymerase complexHydrogen-deuterium exchangeSubunit interfaceProcapsidRNA loadingBiochemical studiesMolecular motorsEmpty capsidsHexamerViral capsidCapsidMass spectrometryGenomeDsRNAProcessivityBacteriophagesInteractionRegulationAssociates
2005
C—H Bond Activation by Iridium and Rhodium Complexes: Catalytic Hydrogen—Deuterium Exchange and C—C Bond‐Forming Reactions
Klei S, Tan K, Golden J, Yung C, Thalji R, Ahrendt K, Ellman J, Tilley T, Bergman R. C—H Bond Activation by Iridium and Rhodium Complexes: Catalytic Hydrogen—Deuterium Exchange and C—C Bond‐Forming Reactions. ChemInform 2005, 36: no-no. DOI: 10.1002/chin.200524251.Peer-Reviewed Original Research
2003
Online Hydrogen-Deuterium Exchange and a Tandem-Quadrupole Time-of-Flight Mass Spectrometer Coupled with Liquid Chromatography for Metabolite Identification in Drug Metabolism*
Nassar A. Online Hydrogen-Deuterium Exchange and a Tandem-Quadrupole Time-of-Flight Mass Spectrometer Coupled with Liquid Chromatography for Metabolite Identification in Drug Metabolism*. Journal Of Chromatographic Science 2003, 41: 398-404. PMID: 14558931, DOI: 10.1093/chromsci/41.8.398.Peer-Reviewed Original ResearchConceptsMetabolite identificationMobile phaseHydrogen-deuterium (H-D) exchangeH-D exchange processTime-of-flight mass spectrometerDemethylation of methoxy groupsHydroxylation of methyl groupsH-D exchangeHydrogen-deuterium exchangeIdentification of metabolitesLiquid chromatographyMethoxy groupEster groupsMethyl groupMetabolite elucidationMass spectrometerHuman hepatic microsomesD(2)ODrug discoveryDehydrogenationExchange processRetention timeEquilibration timeOxidationNo significant difference
2000
Design of single-layer β-sheets without a hydrophobic core
Koide S, Huang X, Link K, Koide A, Bu Z, Engelman D. Design of single-layer β-sheets without a hydrophobic core. Nature 2000, 403: 456-460. PMID: 10667801, DOI: 10.1038/35000255.Peer-Reviewed Original ResearchConceptsSingle-layer β-sheetΒ-sheetHydrophobic coreΒ-sheet segmentsProtein foldingHydrogen-deuterium exchangeOuter surface protein AΒ-sheet structureChemical denaturationSmall-angle X-rayProtein AFoldingMain thermodynamic driving forceSurface protein ABorrelia burgdorferiNuclear magnetic resonanceThermodynamic driving forceMisfoldingNonpolar moietiesHydrophobic effectSolvent resultsProteinAdjacent unitsDenaturationVariants
1997
Native-like structure of a protein-folding intermediate bound to the chaperonin GroEL
Goldberg M, Zhang J, Sondek S, Matthews C, Fox R, Horwich A. Native-like structure of a protein-folding intermediate bound to the chaperonin GroEL. Proceedings Of The National Academy Of Sciences Of The United States Of America 1997, 94: 1080-1085. PMID: 9037009, PMCID: PMC19747, DOI: 10.1073/pnas.94.4.1080.Peer-Reviewed Original ResearchConceptsNative-like structureChaperonin GroELDihydrofolate reductaseProtein-folding intermediatesNative dihydrofolate reductaseStopped-flow fluorescence experimentsNonnative proteinsSubstrate proteinsProductive foldingPresence of ATPHuman dihydrofolate reductaseHydrogen-deuterium exchangeGroELPrimary structureProteinCentral channelHydrophobic interactionsFluorescence experimentsGroESFoldingSpeciesReductaseNMR spectroscopyDistant partsATP
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