2021
Pharmacological inhibition of PI5P4Kα/β disrupts cell energy metabolism and selectively kills p53-null tumor cells
Chen S, Tjin C, Gao X, Xue Y, Jiao H, Zhang R, Wu M, He Z, Ellman J, Ha Y. Pharmacological inhibition of PI5P4Kα/β disrupts cell energy metabolism and selectively kills p53-null tumor cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2002486118. PMID: 34001596, PMCID: PMC8166193, DOI: 10.1073/pnas.2002486118.Peer-Reviewed Original ResearchMeSH KeywordsAMP-Activated Protein Kinase KinasesAnimalsEnergy MetabolismHumansInsulinInsulin Receptor Substrate ProteinsMechanistic Target of Rapamycin Complex 1MiceMuscle Fibers, SkeletalNeoplasmsPhosphorylationPhosphotransferases (Alcohol Group Acceptor)Ribosomal Protein S6 Kinases, 70-kDaSignal TransductionSmall Molecule LibrariesTumor Suppressor Protein p53ConceptsP53-null tumor cellsMost human cancer cellsCell energy homeostasisCell energy metabolismTumor suppressor genePI5P4KHuman cancer cellsGenetic experimentsDifferentiated myotubesAMPK activationStructural basisKinase activityEnergy stressMetabolic regulationSuppressor geneFunction mutationsLate-onset tumorsSubstrate loopP53 tumor suppressor geneChemical probesPI3KCell typesExquisite specificityEnergy metabolismTumor cells
2020
Structural elucidation of the cis-prenyltransferase NgBR/DHDDS complex reveals insights in regulation of protein glycosylation
Edani BH, Grabińska KA, Zhang R, Park EJ, Siciliano B, Surmacz L, Ha Y, Sessa WC. Structural elucidation of the cis-prenyltransferase NgBR/DHDDS complex reveals insights in regulation of protein glycosylation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 20794-20802. PMID: 32817466, PMCID: PMC7456142, DOI: 10.1073/pnas.2008381117.Peer-Reviewed Original ResearchConceptsActive site tunnelProtein glycosylationAtomic resolution structuresGlycosyl carrier lipidsΑ3 helixEnzyme active sitePTase activityResolution structureActive siteEndoplasmic reticulumHomodimeric formCarrier lipidRate-limiting stepGlycosylationCrystal structureDHDDSStructural elucidationPTaseIsoprene chainPrenyltransferaseUnique insightsComplexesUnfavorable stateNgBRHomodimeric
2015
Resolution of structure of PIP5K1A reveals molecular mechanism for its regulation by dimerization and dishevelled
Hu J, Yuan Q, Kang X, Qin Y, Li L, Ha Y, Wu D. Resolution of structure of PIP5K1A reveals molecular mechanism for its regulation by dimerization and dishevelled. Nature Communications 2015, 6: 8205. PMID: 26365782, PMCID: PMC4570271, DOI: 10.1038/ncomms9205.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsBinding SitesCalorimetryCatalytic DomainCircular DichroismCrystallizationCrystallography, X-RayDimerizationDishevelled ProteinsHEK293 CellsHumansPhosphatidylinositol 4,5-DiphosphatePhosphatidylinositol PhosphatesPhosphoproteinsPhosphorylationPhosphotransferases (Alcohol Group Acceptor)Protein Structure, TertiaryZebrafishConceptsSubstrate-binding siteLipid kinasesDIX domainCellular functionsCatalytic domainPhosphate kinaseÅ resolutionMutagenesis studiesRegulatory mechanismsMolecular mechanismsCatalytic activityPIP5K1AHead groupsCrystal structureSide dimerKinaseWntStructural informationRegulationDimerizationMoleculesResolution of structuresImportant rolePhosphatidylinositolType I
2004
The X-Ray Structure of an Antiparallel Dimer of the Human Amyloid Precursor Protein E2 Domain
Wang Y, Ha Y. The X-Ray Structure of an Antiparallel Dimer of the Human Amyloid Precursor Protein E2 Domain. Molecular Cell 2004, 15: 343-353. PMID: 15304215, DOI: 10.1016/j.molcel.2004.06.037.Peer-Reviewed Original ResearchConceptsMembrane protein precursorsX-ray structureSpectrin familyHeparan sulfate proteoglycanDimer interfaceBiological functionsStructure of E2Protein structureProtein precursorPutative ligandE2 domainContinuous helixExtracellular matrixUnexpected resemblanceAntiparallel dimerSulfate proteoglycanAntiparallel orientationPrecursor presentDomainBindsHelixDimerizationSecond monomerH1 and H7 influenza haemagglutinin structures extend a structural classification of haemagglutinin subtypes
Russell R, Gamblin S, Haire L, Stevens D, Xiao B, Ha Y, Skehel J. H1 and H7 influenza haemagglutinin structures extend a structural classification of haemagglutinin subtypes. Virology 2004, 325: 287-296. PMID: 15246268, DOI: 10.1016/j.virol.2004.04.040.Peer-Reviewed Original ResearchThe Structure and Receptor Binding Properties of the 1918 Influenza Hemagglutinin
Gamblin S, Haire L, Russell R, Stevens D, Xiao B, Ha Y, Vasisht N, Steinhauer D, Daniels R, Elliot A, Wiley D, Skehel J. The Structure and Receptor Binding Properties of the 1918 Influenza Hemagglutinin. Science 2004, 303: 1838-1842. PMID: 14764886, DOI: 10.1126/science.1093155.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBinding SitesBirdsCrystallography, X-RayHemagglutinin Glycoproteins, Influenza VirusHistory, 20th CenturyHumansHydrogen BondingInfluenza A virusInfluenza, HumanMembrane GlycoproteinsModels, MolecularMolecular Sequence DataProtein ConformationProtein Structure, TertiaryReceptors, VirusSequence AlignmentSialic AcidsSpecies SpecificitySwine
2001
X-ray structures of H5 avian and H9 swine influenza virus hemagglutinins bound to avian and human receptor analogs
Ha Y, Stevens D, Skehel J, Wiley D. X-ray structures of H5 avian and H9 swine influenza virus hemagglutinins bound to avian and human receptor analogs. Proceedings Of The National Academy Of Sciences Of The United States Of America 2001, 98: 11181-11186. PMID: 11562490, PMCID: PMC58807, DOI: 10.1073/pnas.201401198.Peer-Reviewed Original Research