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 ResearchMeSH KeywordsBinding SitesBromineCrystallography, X-RayHEK293 CellsHeLa CellsHumansParoxetineProtein BindingSelective Serotonin Reuptake InhibitorsSerotonin Plasma Membrane Transport Proteins
2018
Computation-guided analysis of paroxetine binding to hSERT reveals functionally important structural elements and dynamics
Abramyan AM, Slack RD, Meena S, Davis BA, Newman AH, Singh SK, Shi L. Computation-guided analysis of paroxetine binding to hSERT reveals functionally important structural elements and dynamics. Neuropharmacology 2018, 161: 107411. PMID: 30391505, PMCID: PMC6494725, DOI: 10.1016/j.neuropharm.2018.10.040.Peer-Reviewed Original ResearchMeSH KeywordsBiological Transport, ActiveEntropyHumansKineticsModels, MolecularMolecular Dynamics SimulationMutationParoxetineProtein BindingProtein ConformationSelective Serotonin Reuptake InhibitorsSerotonin Plasma Membrane Transport Proteins
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
2014
Structure and Regulatory Interactions of the Cytoplasmic Terminal Domains of Serotonin Transporter
Fenollar-Ferrer C, Stockner T, Schwarz TC, Pal A, Gotovina J, Hofmaier T, Jayaraman K, Adhikary S, Kudlacek O, Mehdipour AR, Tavoulari S, Rudnick G, Singh SK, Konrat R, Sitte HH, Forrest LR. Structure and Regulatory Interactions of the Cytoplasmic Terminal Domains of Serotonin Transporter. Biochemistry 2014, 53: 5444-5460. PMID: 25093911, PMCID: PMC4147951, DOI: 10.1021/bi500637f.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceCircular DichroismCytoplasmFluorescence Resonance Energy TransferHumansMagnetic Resonance SpectroscopyModels, MolecularMolecular Sequence DataProtein ConformationProtein FoldingProtein Structure, SecondaryProtein Structure, TertiarySerotonin Plasma Membrane Transport ProteinsConceptsTerminal domainStructures of homologuesYellow fluorescent protein tagProtein-protein interactionsFluorescent protein tagsFluorescence resonance energy transfer signalN-terminal domainCarboxy-terminal endHelix-breaking residuesCyan fluorescent proteinEnergy transfer signalHuman serotonin transporterNSS familyConformational cycleCircular dichroism spectroscopyProtein tagsCytoplasmic segmentRegulatory interactionsTransmembrane regionUptake of neurotransmittersInteraction partnersRegulatory mechanismsSerotonin transporterBiophysical approachesFluorescent protein