A Competitive Inhibitor Traps LeuT in an Open-to-Out Conformation
Singh SK, Piscitelli CL, Yamashita A, Gouaux E. A Competitive Inhibitor Traps LeuT in an Open-to-Out Conformation. Science 2008, 322: 1655-1661. PMID: 19074341, PMCID: PMC2832577, DOI: 10.1126/science.1166777.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid Transport SystemsAmino AcidsBacterial ProteinsBinding SitesBinding, CompetitiveBiological TransportCrystallizationCrystallography, X-RayHydrogen BondingHydrophobic and Hydrophilic InteractionsKineticsLeucineLigandsModels, BiologicalModels, MolecularProtein ConformationProtein Structure, TertiarySodiumSymportersTryptophanConceptsNeurotransmitter sodium symportersPrimary substrate siteAmino acid substratesSodium symportersSecondary transportersExtracellular gateSubstrate passageLeucine transporterArginine 30Substrate transportCellular membranesConformational changesAcid substratesConformational statesSubstrate siteFunctional studiesIon gradientsLeuTWeak binding sitesTransportersBinding sitesSmall moleculesCompetitive inhibitorConformationTrp complexStructural models of inhibition in neurotransmitter sodium symporters
Singh S, Gouaux J. Structural models of inhibition in neurotransmitter sodium symporters. The FASEB Journal 2008, 22: 254.2-254.2. DOI: 10.1096/fasebj.22.1_supplement.254.2.Peer-Reviewed Original ResearchNeurotransmitter sodium symportersSodium symportersNovel noncompetitive inhibitorsX-ray crystallographyAtomic-level insightsSteady-state kinetic dataLeucine transporterSteady-state kineticsMolecular principlesRational designSmall moleculesIon gradientsKinetic dataDissociation assaysAddictive compoundInhibitor actionCritical roleNoncompetitive modeStructural paradigmSymporterNoncompetitive inhibitorAllosteric antagonistsGlial cytoplasmSynaptic transmissionLeuT