2021
Structure-guided design of a perampanel-derived pharmacophore targeting the SARS-CoV-2 main protease
Deshmukh MG, Ippolito JA, Zhang CH, Stone EA, Reilly RA, Miller SJ, Jorgensen WL, Anderson KS. Structure-guided design of a perampanel-derived pharmacophore targeting the SARS-CoV-2 main protease. Structure 2021, 29: 823-833.e5. PMID: 34161756, PMCID: PMC8218531, DOI: 10.1016/j.str.2021.06.002.Peer-Reviewed Original ResearchConceptsMain proteaseSARS-CoV-2 main proteaseActive site flexibilityDetailed structural insightsStructure-activity relationshipsInhibitor design effortsLow micromolar rangeActive site cysteineChemical scaffoldsLow nanomolar rangeCovalent adductsStructure-guided designCrystal structureStructural insightsPharmacophoreAdductsAttractive targetScaffoldsCysteineAnaloguesMechanism of actionSupRangeStructure
2017
Glutathione-Responsive Selenosulfide Prodrugs as a Platform Strategy for Potent and Selective Mechanism-Based Inhibition of Protein Tyrosine Phosphatases
Tjin CC, Otley KD, Baguley TD, Kurup P, Xu J, Nairn AC, Lombroso PJ, Ellman JA. Glutathione-Responsive Selenosulfide Prodrugs as a Platform Strategy for Potent and Selective Mechanism-Based Inhibition of Protein Tyrosine Phosphatases. ACS Central Science 2017, 3: 1322-1328. PMID: 29296673, PMCID: PMC5746864, DOI: 10.1021/acscentsci.7b00486.Peer-Reviewed Original ResearchStriatal-enriched protein tyrosine phosphataseProtein tyrosineTyrosine phosphatasePhosphatase inhibitorProtein tyrosine phosphataseProtein tyrosine phosphorylation levelsActive site cysteineProtein tyrosine phosphorylationTyrosine phosphorylation levelsHuman PTPsSite cysteinePTP targetsTyrosine phosphorylationRepresentative cysteine proteaseCysteine proteasesHuman diseasesCellular activitiesPhosphorylation levelsVirulence factorsEssential roleSelective mechanismIntracellular GSH concentrationSelective active sitesNeurodegenerative diseasesPTP
2007
Structure of a Herpesvirus-Encoded Cysteine Protease Reveals a Unique Class of Deubiquitinating Enzymes
Schlieker C, Weihofen WA, Frijns E, Kattenhorn LM, Gaudet R, Ploegh HL. Structure of a Herpesvirus-Encoded Cysteine Protease Reveals a Unique Class of Deubiquitinating Enzymes. Molecular Cell 2007, 25: 677-687. PMID: 17349955, PMCID: PMC7110467, DOI: 10.1016/j.molcel.2007.01.033.Peer-Reviewed Original ResearchConceptsDeubiquitinating enzymePapain-like foldCysteine protease domainLarge tegument proteinActive site cysteineActive site residuesBeta-hairpin loopExtensive hydrophobic interactionsSuicide substrateProtease moduleProtease domainTegument proteinsCysteine proteasesHairpin loopEnzymeThioether linkageUbUnique classHydrophobic interactionsMurine cytomegalovirusUbiquitinDomainProteinMembersCrystal structure
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