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
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
2013
Radioligand Binding to Nanodisc-Reconstituted Membrane Transporters Assessed by the Scintillation Proximity Assay
Nasr ML, Singh SK. Radioligand Binding to Nanodisc-Reconstituted Membrane Transporters Assessed by the Scintillation Proximity Assay. Biochemistry 2013, 53: 4-6. PMID: 24344975, PMCID: PMC4062192, DOI: 10.1021/bi401412e.Peer-Reviewed Original ResearchConceptsMembrane transportersPhospholipid bilayer nanodiscsNative cell membranesSecondary transportersScintillation proximityBilayer nanodiscsDetergent solubilizationCell membraneLipid vesiclesTransportersNanodiscsScreening effortsBackground interferenceLeuTProteinVesiclesPowerful techniqueBindingMembraneReconstitutionRadioligand bindingSolubilizationInterferencePotential challengesProximity
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