2025
Structure of mitochondrial pyruvate carrier and its inhibition mechanism
He Z, Zhang J, Xu Y, Fine E, Suomivuori C, Dror R, Feng L. Structure of mitochondrial pyruvate carrier and its inhibition mechanism. Nature 2025, 641: 250-257. PMID: 40044865, PMCID: PMC12043432, DOI: 10.1038/s41586-025-08667-y.Peer-Reviewed Original ResearchConceptsMitochondrial pyruvate carrierPyruvate carrierMPC functionSubstrate-binding siteCytosolic glycolysisCentral metaboliteTranslocation pathwayCellular metabolismMolecular basisMetabolic gatekeeperMolecular mechanismsConformational statesInhibition mechanismTherapeutic reagentsTransport functionCritical roleStructural findingsNon-alcoholic steatohepatitisInhibitionTranslocationGlycolysisPathwayBindingMetabolismPhysiologyStructural basis for the transport and regulation mechanism of the multidrug resistance-associated protein 2
Koide E, Pietz H, Beltran J, Chen J. Structural basis for the transport and regulation mechanism of the multidrug resistance-associated protein 2. Nature Communications 2025, 16: 484. PMID: 39779684, PMCID: PMC11711199, DOI: 10.1038/s41467-024-55810-w.Peer-Reviewed Original ResearchConceptsAutoinhibited stateR domainPost-translocation stateSubstrate-binding sitePre-translocation stateATP-binding siteProtein 2Nucleotide-binding domain 2Cryogenic electron microscopyStructural basisDiverse array of compoundsDomain 2Cryo-EMRegulation mechanismChemotherapeutic resistanceConformational changesMultidrug resistanceArray of compoundsDiverse arrayConformational statesLiver homeostasisMultidrug resistance-associated protein 2Initial transportSubstrateCytosol
2024
Structural insights into PPP2R5A degradation by HIV-1 Vif
Hu Y, Delviks-Frankenberry K, Wu C, Arizaga F, Pathak V, Xiong Y. Structural insights into PPP2R5A degradation by HIV-1 Vif. Nature Structural & Molecular Biology 2024, 31: 1492-1501. PMID: 38789685, DOI: 10.1038/s41594-024-01314-6.Peer-Reviewed Original ResearchHost-virus protein interactionsCullin RING E3 ubiquitin ligasesInduced G2/M cell cycle arrestSets of proteinsG2/M cell cycle arrestSubstrate-binding siteCryogenic-electron microscopy structuresProtein phosphatase 2ADegradation-independent mechanismCell cycle arrestUbiquitin ligaseProtein interactionsPhosphatase 2AAntiviral proteinCycle arrestDegradation-dependentA-resolutionHIV-1 VifPPP2R5AStructural insightsDiverse interactionsProteinCellular studiesPhosphatase activityPotential target
2022
Molecular basis for integrin adhesion receptor binding to p21-activated kinase 4 (PAK4)
Ha B, Yigit S, Natarajan N, Morse E, Calderwood D, Boggon T. Molecular basis for integrin adhesion receptor binding to p21-activated kinase 4 (PAK4). Communications Biology 2022, 5: 1257. PMID: 36385162, PMCID: PMC9669019, DOI: 10.1038/s42003-022-04157-3.Peer-Reviewed Original ResearchConceptsP21-activated kinase 4Integrin adhesion receptorsMolecular basisAdhesion receptorsIntegrin β5Potential cellular rolesIntegrin β tailsKinase 4Membrane-proximal halfSubstrate-binding grooveSubstrate-binding siteSite-directed mutagenesisCellular rolesPhosphoacceptor sitesΒ tailExtracellular ligandsCytoplasmic signalingCytoplasmic tailKinase domainMultiple kinasesIntegrin complexΒ5 integrinsΒ5TailMutagenesis
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
2012
Assessing the range of kinase autoinhibition mechanisms in the insulin receptor family
Artim SC, Mendrola JM, Lemmon MA. Assessing the range of kinase autoinhibition mechanisms in the insulin receptor family. Biochemical Journal 2012, 448: 213-220. PMID: 22992069, PMCID: PMC3492919, DOI: 10.1042/bj20121365.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid MotifsAmino Acid SequenceAntigens, CDCatalytic DomainCrystallography, X-RayEnzyme ActivationHumansIn Vitro TechniquesModels, MolecularMutationNeoplasmsProtein Structure, QuaternaryReceptor Tyrosine Kinase-like Orphan ReceptorsReceptor, InsulinReceptor, trkARecombinant ProteinsThe Mechanistic Basis for Noncompetitive Ibogaine Inhibition of Serotonin and Dopamine Transporters*
Bulling S, Schicker K, Zhang YW, Steinkellner T, Stockner T, Gruber CW, Boehm S, Freissmuth M, Rudnick G, Sitte HH, Sandtner W. The Mechanistic Basis for Noncompetitive Ibogaine Inhibition of Serotonin and Dopamine Transporters*. Journal Of Biological Chemistry 2012, 287: 18524-18534. PMID: 22451652, PMCID: PMC3365767, DOI: 10.1074/jbc.m112.343681.Peer-Reviewed Original ResearchConceptsSubstrate-induced currentsCell exteriorPermeation pathwayCytoplasmic permeation pathwaysSubstrate-binding site
1994
Effect of tyrosine kinase inhibition on basal and epidermal growth factor‐stimulated human Caco‐2 enterocyte sheet migration and proliferation
Basson M, Turowski G, Zarif A, Modlin I, Beidler D, Jena B, Madri J. Effect of tyrosine kinase inhibition on basal and epidermal growth factor‐stimulated human Caco‐2 enterocyte sheet migration and proliferation. Journal Of Cellular Physiology 1994, 160: 491-501. PMID: 8077287, DOI: 10.1002/jcp.1041600312.Peer-Reviewed Original ResearchConceptsEpidermal growth factorTyrosine kinaseTyrosine kinase regulationEGF-stimulated migrationProtein-linked DNA breaksSubstrate-binding siteTyrosine kinase inhibitor genisteinCell-matrix interactionsDNA topoisomerase activityKinase inhibitor genisteinKinase regulationATP bindingMonolayer expansionEGF stimulationSheet migrationSubunit organizationDNA breaksTopoisomerase activityEGF receptorInhibitor genisteinCell migrationCell proliferationKinase inhibitionTyrosine kinase inhibitionKinase
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