2019
A Novel Bromine-Containing Paroxetine Analogue Provides Mechanistic Clues for Binding Ambiguity at the Central Primary Binding Site of the Serotonin Transporter
Slack RD, Abramyan AM, Tang H, Meena S, Davis BA, Bonifazi A, Giancola JB, Deschamps JR, Naing S, Yano H, Singh SK, Newman AH, Shi L. A Novel Bromine-Containing Paroxetine Analogue Provides Mechanistic Clues for Binding Ambiguity at the Central Primary Binding Site of the Serotonin Transporter. ACS Chemical Neuroscience 2019, 10: 3946-3952. PMID: 31424193, PMCID: PMC8272913, DOI: 10.1021/acschemneuro.9b00375.Peer-Reviewed Original Research
2016
Mechanism of Paroxetine (Paxil) Inhibition of the Serotonin Transporter
Davis BA, Nagarajan A, Forrest LR, Singh SK. Mechanism of Paroxetine (Paxil) Inhibition of the Serotonin Transporter. Scientific Reports 2016, 6: 23789. PMID: 27032980, PMCID: PMC4817154, DOI: 10.1038/srep23789.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBinding SitesCells, CulturedChickensCocaineDopamine Plasma Membrane Transport ProteinsDrosophila melanogasterDrosophila ProteinsModels, MolecularMolecular ConformationMolecular Docking SimulationParoxetineProtein ConformationRadioligand AssaySelective Serotonin Reuptake InhibitorsSequence AlignmentSequence Homology, Amino AcidSerotoninSerotonin Plasma Membrane Transport ProteinsConceptsIntegral membrane proteinsDrosophila melanogaster dopamine transporterSERT homology modelMembrane proteinsSerotonin transporterMolecular insightsHomology modelIon gradientsFlux assaysTransportersSERT substratesPotassium ion gradientSignificant clinical attentionPresynaptic neuronsDopamine transporterProteinUnfavorable movementSitesSynaptic serotoninBindingSubstrateAssaysRadioligand bindingInhibitorsPotent selective serotonin reuptake inhibitor
2009
Crystal structure and association behaviour of the GluR2 amino‐terminal domain
Jin R, Singh SK, Gu S, Furukawa H, Sobolevsky AI, Zhou J, Jin Y, Gouaux E. Crystal structure and association behaviour of the GluR2 amino‐terminal domain. The EMBO Journal 2009, 28: 1812-1823. PMID: 19461580, PMCID: PMC2699365, DOI: 10.1038/emboj.2009.140.Peer-Reviewed Original ResearchConceptsAmino-terminal domainLigand-gated ion channel proteinsReceptor assemblyModular domain architectureIon channel proteinsFast excitatory neurotransmissionSame subfamilyMolecular basisReceptor subfamiliesChannel proteinsMolecular processesSubfamiliesAMPA receptor GluR1Ionotropic glutamate receptorsCrystal structureExcitatory neurotransmissionAssemblyGlutamate receptorsPropose mechanismsReceptorsSubunitsDomainProteinAssemblagesNMDA receptors
2008
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 complex
2007
Antidepressant binding site in a bacterial homologue of neurotransmitter transporters
Singh SK, Yamashita A, Gouaux E. Antidepressant binding site in a bacterial homologue of neurotransmitter transporters. Nature 2007, 448: 952-956. PMID: 17687333, DOI: 10.1038/nature06038.Peer-Reviewed Original Research
2005
Subunit arrangement and function in NMDA receptors
Furukawa H, Singh SK, Mancusso R, Gouaux E. Subunit arrangement and function in NMDA receptors. Nature 2005, 438: 185-192. PMID: 16281028, DOI: 10.1038/nature04089.Peer-Reviewed Original ResearchConceptsHeteromeric ion channelsNR1-NR2AMammalian central nervous systemSlow channel openingChannel openingHeterodimer interfaceTransduction cascadeIon channel openingSubunit arrangementSubunit interfaceIon channelsNR2 subunitsReceptor functionChannel deactivationNMDA receptorsNMDA receptor functionReceptorsExcitatory neurotransmissionFunctional unitsCentral nervous systemNR1GlutamateGlycineNervous systemHeterodimersCrystal structure of a bacterial homologue of Na+/Cl--dependent neurotransmitter transporters
Yamashita A, Singh SK, Kawate T, Jin Y, Gouaux E. Crystal structure of a bacterial homologue of Na+/Cl--dependent neurotransmitter transporters. Nature 2005, 437: 215-223. PMID: 16041361, DOI: 10.1038/nature03978.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceBacteriaBacterial ProteinsBinding SitesBiological TransportChloridesCrystallography, X-RayHydrophobic and Hydrophilic InteractionsLeucineMembrane Transport ProteinsModels, MolecularMolecular Sequence DataNeurotransmitter AgentsSequence AlignmentSodiumStructure-Activity RelationshipWaterConceptsBacterial homologueProtein coreDependent neurotransmitter transportersTransmembrane helicesTransmembrane segmentsAquifex aeolicusUptake of neurotransmittersSubstrate bindingNeurotransmitter transportersMain-chain atomsMembrane bilayerDependent transportersElectrochemical gradientIon binding siteTransportersHelix dipole