2020
Improving the Pharmacodynamics and In Vivo Activity of ENPP1‐Fc Through Protein and Glycosylation Engineering
Stabach PR, Zimmerman K, Adame A, Kavanagh D, Saeui CT, Agatemor C, Gray S, Cao W, De La Cruz EM, Yarema KJ, Braddock DT. Improving the Pharmacodynamics and In Vivo Activity of ENPP1‐Fc Through Protein and Glycosylation Engineering. Clinical And Translational Science 2020, 14: 362-372. PMID: 33064927, PMCID: PMC7877847, DOI: 10.1111/cts.12887.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArea Under CurveDisease Models, AnimalEnzyme Replacement TherapyGlycosylationHalf-LifeHistocompatibility Antigens Class IHumansMaleMice, TransgenicPhosphoric Diester HydrolasesProtein EngineeringProtein Structure, TertiaryPyrophosphatasesReceptors, FcRecombinant Fusion ProteinsVascular CalcificationConceptsProtein engineeringO-BuN-glycansGlycosylation engineeringCellular recyclingENPP1-deficient miceTerminal sialylationBiomanufacturing platformProtein therapeuticsCalcification disordersSialylationCellsVivo activityFc neonatal receptorTherapeuticsArterial calcificationProteinMurine modelManNAcEnzyme replacementNeonatal receptorEfficacious levelsGeneral strategyThree-prong strategyDrug potency
2013
Molecular Basis of Purinergic Signal Metabolism by Ectonucleotide Pyrophosphatase/Phosphodiesterases 4 and 1 and Implications in Stroke*♦
Albright RA, Ornstein DL, Cao W, Chang WC, Robert D, Tehan M, Hoyer D, Liu L, Stabach P, Yang G, De La Cruz EM, Braddock DT. Molecular Basis of Purinergic Signal Metabolism by Ectonucleotide Pyrophosphatase/Phosphodiesterases 4 and 1 and Implications in Stroke*♦. Journal Of Biological Chemistry 2013, 289: 3294-3306. PMID: 24338010, PMCID: PMC3916532, DOI: 10.1074/jbc.m113.505867.Peer-Reviewed Original ResearchConceptsExtracellular membrane proteinsMembrane proteinsSubstrate specificityMolecular basisHigh-resolution crystal structuresResolution crystal structureComparative structural analysisATP hydrolysisNPP1Brain vascular endotheliumCorresponding regionTerminal phosphateLow nanomolar concentrationsPurinergic signalsPlatelet aggregationProteinATPEnzymeNanomolar concentrationsVascular endotheliumPhosphodiesterases 4Ap3AMetabolismSurface of chondrocytesTissue mineralization
2004
NMR-Driven Discovery of Benzoylanthranilic Acid Inhibitors of Far Upstream Element Binding Protein Binding to the Human Oncogene c-myc Promoter
Huth JR, Yu L, Collins I, Mack J, Mendoza R, Isaac B, Braddock DT, Muchmore SW, Comess KM, Fesik SW, Clore GM, Levens D, Hajduk PJ. NMR-Driven Discovery of Benzoylanthranilic Acid Inhibitors of Far Upstream Element Binding Protein Binding to the Human Oncogene c-myc Promoter. Journal Of Medicinal Chemistry 2004, 47: 4851-4857. PMID: 15369388, DOI: 10.1021/jm0497803.Peer-Reviewed Original ResearchMeSH KeywordsBinding SitesCombinatorial Chemistry TechniquesDNA HelicasesDNA-Binding ProteinsDNA, Single-StrandedDrug DesignGenes, mycHumansInhibitory Concentration 50LigandsMagnetic Resonance SpectroscopyModels, MolecularPromoter Regions, GeneticProtein ConformationProtein Structure, TertiaryProto-Oncogene MasRepetitive Sequences, Amino AcidRNA-Binding ProteinsStructure-Activity RelationshipConceptsUpstream element binding proteinC-myc expressionElement-binding proteinC-Myc pathwayTranscription factorsBinding proteinHost of proteinsRelated transcription factorsAberrant gene expressionC-myc promoterGel shift analysisSlow cell growthC-myc regulationProto-oncogene c-mycFBP bindsKH domainsFBP functionInhibits DNADevelopment of therapeuticsOwn expressionGene expressionHydrophobic pocketC-MycBinding pocketsCell growth
2002
Molecular basis of sequence‐specific single‐stranded DNA recognition by KH domains: solution structure of a complex between hnRNP K KH3 and single‐stranded DNA
Braddock DT, Baber JL, Levens D, Clore GM. Molecular basis of sequence‐specific single‐stranded DNA recognition by KH domains: solution structure of a complex between hnRNP K KH3 and single‐stranded DNA. The EMBO Journal 2002, 21: 3476-3485. PMID: 12093748, PMCID: PMC126100, DOI: 10.1093/emboj/cdf352.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid MotifsAmino Acid SequenceBase SequenceCrystallography, X-RayDNA HelicasesDNA, Single-StrandedDNA-Binding ProteinsHeterogeneous-Nuclear Ribonucleoprotein KHeterogeneous-Nuclear RibonucleoproteinsHumansHydrogen BondingModels, MolecularMolecular Sequence DataNuclear Magnetic Resonance, BiomolecularNucleic Acid ConformationProtein BindingProtein ConformationProtein Structure, TertiaryRibonucleoproteinsRNA-Binding ProteinsSequence AlignmentSequence Homology, Amino AcidSolutionsSubstrate SpecificityConceptsKH domainsDNA recognitionHeterogeneous nuclear ribonucleoprotein KK homology domainSolution structureProtein-ssDNA complexResidues N-terminalHomology domainKH3 domainGXXG motifKH4 domainsMolecular basisN-terminalCytosine basesIsoleucine residueAmino acidsKH3Crucial roleComplexesTetradsDomainDNAMotifMethyl groupResiduesStructure and dynamics of KH domains from FBP bound to single-stranded DNA
Braddock DT, Louis JM, Baber JL, Levens D, Clore GM. Structure and dynamics of KH domains from FBP bound to single-stranded DNA. Nature 2002, 415: 1051-1056. PMID: 11875576, DOI: 10.1038/4151051a.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceDNA HelicasesDNA, Single-StrandedDNA-Binding ProteinsGene Expression RegulationGenes, mycHumansHydrogen BondingMacromolecular SubstancesMagnetic Resonance SpectroscopyModels, MolecularMolecular Sequence DataNucleic Acid ConformationProtein BindingProtein ConformationProtein FoldingProtein Structure, TertiaryRNA-Binding Proteins
2001
Rapid Identification of Medium- to Large-Scale Interdomain Motion in Modular Proteins Using Dipolar Couplings
Braddock D, Cai M, Baber J, Huang Y, Clore G. Rapid Identification of Medium- to Large-Scale Interdomain Motion in Modular Proteins Using Dipolar Couplings. Journal Of The American Chemical Society 2001, 123: 8634-8635. PMID: 11525687, DOI: 10.1021/ja016234f.Peer-Reviewed Original ResearchMeSH KeywordsDNADNA-Binding ProteinsMembrane ProteinsNuclear Magnetic Resonance, BiomolecularNuclear ProteinsProtein FoldingProtein Structure, TertiaryConceptsLarge-scale interdomain motions
2000
Biophysical Characterization of gp41 Aggregates Suggests a Model for the Molecular Mechanism of HIV-associated Neurological Damage and Dementia*
Caffrey M, Braddock D, Louis J, Abu-Asab M, Kingma D, Liotta L, Tsokos M, Tresser N, Pannell L, Watts N, Steven A, Simon M, Stahl S, Wingfield P, Clore G. Biophysical Characterization of gp41 Aggregates Suggests a Model for the Molecular Mechanism of HIV-associated Neurological Damage and Dementia*. Journal Of Biological Chemistry 2000, 275: 19877-19882. PMID: 10747981, DOI: 10.1074/jbc.m001036200.Peer-Reviewed Original ResearchMeSH KeywordsAIDS Dementia ComplexBrainBrain DiseasesChromatography, GelEndopeptidasesExtracellular SpaceHIV Envelope Protein gp41HIV SeropositivityHumansHydrogen-Ion ConcentrationImmunohistochemistryMembrane GlycoproteinsMicroscopy, ElectronProtein BindingProtein Structure, TertiaryRetroviridae ProteinsConceptsNeurological damageBrains of HIVHuman immunodeficiency virusImmunodeficiency virusEnvelope protein gp41HIVBrain tissueDementiaHigh molecular weight formExtracellular aggregatesMolecular weight formsSimian immunodeficiency virus gp41Gp41Molecular mechanismsWeight formsHIV gp41HIV envelope protein gp41Extracellular ectodomainBiochemical methodsDamagePatientsImmunohistochemistryHigh molecular weight aggregatesBrain