2023
A macrocyclic peptide inhibitor traps MRP1 in a catalytically incompetent conformation
Pietz H, Abbas A, Johnson Z, Oldham M, Suga H, Chen J. A macrocyclic peptide inhibitor traps MRP1 in a catalytically incompetent conformation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2220012120. PMID: 36893260, PMCID: PMC10089224, DOI: 10.1073/pnas.2220012120.Peer-Reviewed Original ResearchConceptsMultidrug resistance protein 1MRP1 overexpressionSubstrate transportAdenosine triphosphate-binding cassetteCatalytically incompetent conformationStructurally unrelated moleculesCpI1Small molecule inhibitorsAdenosine triphosphatePlasma membraneA-resolutionCryoelectron microscopyCryo-EMUnrelated moleculesConformational changesMultidrug resistanceMRP1 functionProtein 1Macrocyclic peptidesMultidrug transporter P-glycoproteinFlexible sidechainsXenobiotic compoundsNanomolar potencyCellular toxicityTherapeutic candidate
2014
A mechanistic and structural investigation of modified derivatives of the diaryltriazine class of NNRTIs targeting HIV-1 reverse transcriptase
Mislak AC, Frey KM, Bollini M, Jorgensen WL, Anderson KS. A mechanistic and structural investigation of modified derivatives of the diaryltriazine class of NNRTIs targeting HIV-1 reverse transcriptase. Biochimica Et Biophysica Acta 2014, 1840: 2203-2211. PMID: 24726448, PMCID: PMC4061246, DOI: 10.1016/j.bbagen.2014.04.001.Peer-Reviewed Original ResearchConceptsSolvent interfaceStructure-based drug designCatalytic site geometryPhysiochemical propertiesFuture inhibitor developmentTransient-state kinetic analysisImproved pharmacological propertiesImproved pharmacological profileAzine ringPolymerization stepMorpholine derivativesCrystal structureLow nanomolar potencyDrug designSubstituentsStructural investigationsSite geometryImproved physiochemical propertiesNew inhibitorsNanomolar potencyLow nanomolar antiviral activityDerivativesStructural basisStructural analysisNon-nucleoside inhibitors
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