2020
NMR in integrated biophysical drug discovery for RAS: past, present, and future
Marshall C, KleinJan F, Gebregiworgis T, Lee K, Fang Z, Eves B, Liu N, Gasmi-Seabrook G, Enomoto M, Ikura M. NMR in integrated biophysical drug discovery for RAS: past, present, and future. Journal Of Biomolecular NMR 2020, 74: 531-554. PMID: 32804298, DOI: 10.1007/s10858-020-00338-6.Peer-Reviewed Original ResearchConceptsGTPase domainProper membrane localizationMultiple signaling cascadesOncogenic Ras mutationsKey downstream effectorDrug discoveryGTPase cycleMembrane localizationRAS proteinsGTP hydrolysisConformational selectionRAS signalingDownstream effectorsSignaling cascadesLipid modificationG12C mutantUpstream regulatorBiophysical approachesSmall proteinsRAS oncogenesDruggable pocketHuman cancersCell growthCovalent inhibitorsPeptidyl inhibitors
2018
Multiplexed Real-Time NMR GTPase Assay for Simultaneous Monitoring of Multiple Guanine Nucleotide Exchange Factor Activities from Human Cancer Cells and Organoids
Gebregiworgis T, Marshall C, Nishikawa T, Radulovich N, Sandí M, Fang Z, Rottapel R, Tsao M, Ikura M. Multiplexed Real-Time NMR GTPase Assay for Simultaneous Monitoring of Multiple Guanine Nucleotide Exchange Factor Activities from Human Cancer Cells and Organoids. Journal Of The American Chemical Society 2018, 140: 4473-4476. PMID: 29543440, DOI: 10.1021/jacs.7b13703.Peer-Reviewed Original ResearchMeSH KeywordsBiological AssayGTP PhosphohydrolasesGuanine Nucleotide Exchange FactorsHEK293 CellsHumansMagnetic Resonance SpectroscopyPancreatic NeoplasmsRhoA GTP-Binding ProteinConceptsGuanine nucleotide exchange factorsRhoA-specific Guanine Nucleotide Exchange FactorGuanine nucleotide exchange factor activityNucleotide exchange factor activityHigher GEF activityNucleotide exchange factorsImportant cellular functionsExchange factor activityExchange of GTPProtein of interestReal-time NMRRNA-seq dataCultured human cellsGEF assaysHuman cancer cellsSmall GTPasesExchange factorGEF activityCellular functionsIsotopic labeling schemesNucleotide exchangeGEF-H1GTPase assaysFunctional analysisHuman cells