2017
Conformational dynamics of a neurotransmitter:sodium symporter in a lipid bilayer
Adhikary S, Deredge DJ, Nagarajan A, Forrest LR, Wintrode PL, Singh SK. Conformational dynamics of a neurotransmitter:sodium symporter in a lipid bilayer. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: e1786-e1795. PMID: 28223522, PMCID: PMC5347597, DOI: 10.1073/pnas.1613293114.Peer-Reviewed Original ResearchConceptsSodium symportersMembrane proteinsMammalian membrane proteinsConformational mechanismIntegral membrane proteinsPhospholipid bilayer nanodiscsSolution spectroscopyDetergent-solubilized stateExtracellular loop 2Site-specific labelingSmall molecule neurotransmittersBilayer nanodiscsHydrogen-deuterium exchangeX-ray crystallographyCysteine accessibilityConformational dynamicsMembrane mimicsMolecular dynamics simulationsLoop 2Endogenous cysteineHelices 1ALeuTLipid bilayersProteinSymporter
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
2015
Chapter Nine Biophysical Approaches to the Study of LeuT, a Prokaryotic Homolog of Neurotransmitter Sodium Symporters
Singh SK, Pal A. Chapter Nine Biophysical Approaches to the Study of LeuT, a Prokaryotic Homolog of Neurotransmitter Sodium Symporters. Methods In Enzymology 2015, 557: 167-198. PMID: 25950965, PMCID: PMC4818570, DOI: 10.1016/bs.mie.2015.01.002.Peer-Reviewed Original ResearchConceptsMultiple integral membrane proteinsSolute carrier 6 (SLC6) familyNeurotransmitter sodium symportersIntegral membrane proteinsAmino acid symporterDependent neurotransmitter transportersEukaryotic counterpartsSodium symportersProkaryotic homologAcid symporterLeuT structureMembrane proteinsNeurotransmitter transportersBiophysical approachesLeuTHomology modelingMechanism of transportSecondary transportAmino acidsLipid bilayersSignificant transportersMechanistic paradigmMolecular dynamics simulationsSymporterProtein
2008
LeuT: A prokaryotic stepping stone on the way to a eukaryotic neurotransmitter transporter structure
Singh SK. LeuT: A prokaryotic stepping stone on the way to a eukaryotic neurotransmitter transporter structure. Channels 2008, 2: 380-389. PMID: 19066470, DOI: 10.4161/chan.2.5.6904.Peer-Reviewed Original ResearchConceptsSodium binding siteSolute carrier 6 (SLC6) familyIntegral membrane proteinsStructure/function studiesBinding sitesCrystal structureEukaryotic counterpartsAccurate homology modelsTransporter structureBacterial membersMembrane proteinsNutrient uptakeSequence identityMolecular insightsConformational changesHomology modelSecondary transportLeuTNeurotransmitter clearanceLipid bilayersSolute moleculesBiochemical dataFunction studiesIon bindingCrucial role