2018
Molecular mechanism underlying the subtype-selectivity of competitive inhibitor NF110 and its distinct potencies in human and rat P2X3 receptors
Li B, Wang J, Cheng X, Liu Y, Yang Y, Yang X, Guo C, Niu Y, Cao P, Lu X, Zhu M, Tian Y, Yu Y. Molecular mechanism underlying the subtype-selectivity of competitive inhibitor NF110 and its distinct potencies in human and rat P2X3 receptors. Science Bulletin 2018, 63: 1616-1625. PMID: 36658853, DOI: 10.1016/j.scib.2018.11.016.Peer-Reviewed Original ResearchP2X3 receptorsP2X receptorsExperimental animalsDifferent P2X receptorsLower bodyRat P2X3 receptorsDistinct potenciesSubtype-selective mannerHuman P2X3 receptorsLF domainInhibitors/modulatorsPreclinical dataClinical trialsAmino acidsEquivalent amino acidsATP-binding pocketClinical researchExtracellular ATPSubstitution of residuesReceptorsCation channelsPharmacological activitiesDorsal fin domainInhibitory efficacyChannel activityDruggable negative allosteric site of P2X3 receptors
Wang J, Wang Y, Cui W, Huang Y, Yang Y, Liu Y, Zhao W, Cheng X, Sun W, Cao P, Zhu M, Wang R, Hattori M, Yu Y. Druggable negative allosteric site of P2X3 receptors. Proceedings Of The National Academy Of Sciences Of The United States Of America 2018, 115: 4939-4944. PMID: 29674445, PMCID: PMC5948998, DOI: 10.1073/pnas.1800907115.Peer-Reviewed Original ResearchConceptsAllosteric siteNegative allosteric siteDruggable allosteric sitesG protein-coupled receptorsAllosteric modulationLeft flipperProtein-coupled receptorsNew drug targetsDorsal fin domainLB domainsClinical trialsP2X receptorsAllosteric changesAllosteric inhibitorsChannel mutantsDrug targetsPhase II clinical trialFunctional studiesFin domainRefractory chronic coughIdiopathic pulmonary fibrosisIon channelsLower bodyX-ray crystallographyNegative allosteric modulation
2014
Relative motions between left flipper and dorsal fin domains favour P2X4 receptor activation
Zhao W, Wang J, Ma X, Yang Y, Liu Y, Huang L, Fan Y, Cheng X, Chen H, Wang R, Yu Y. Relative motions between left flipper and dorsal fin domains favour P2X4 receptor activation. Nature Communications 2014, 5: 4189. PMID: 24943126, DOI: 10.1038/ncomms5189.Peer-Reviewed Original ResearchConceptsAllosteric changesChannel gatingLeft flipperP2X4 receptorDorsal fin domainAllosteric eventsP2X4 receptor activationPhysiological functionsResidues leadFin domainHydrophobic interactionsEssential roleExtracellular ATPFundamental processesZinc bridgesChannel activationReceptor activationDorsal finP2X receptorsReceptorsGatingDomainActivationL217V291