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
2016
Biochemical Classification of Disease-associated Mutants of RAS-like Protein Expressed in Many Tissues (RIT1)*
Fang Z, Marshall C, Yin J, Mazhab-Jafari M, Gasmi-Seabrook G, Smith M, Nishikawa T, Xu Y, Neel B, Ikura M. Biochemical Classification of Disease-associated Mutants of RAS-like Protein Expressed in Many Tissues (RIT1)*. Journal Of Biological Chemistry 2016, 291: 15641-15652. PMID: 27226556, PMCID: PMC4957048, DOI: 10.1074/jbc.m116.714196.Peer-Reviewed Original ResearchConceptsDisease-associated mutationsGTPase cycleIntrinsic GTP hydrolysis rateA57GRIT1 mutationsIntrinsic nucleotide exchange rateDisease-associated mutantsGTP hydrolysis rateNucleotide exchange rateReal-time NMRSmall guanosine triphosphataseHEK293T cellsPulldown assaysGuanosine triphosphataseGTP hydrolysisNoonan syndromeGTPase assaysDivergent residuesRIT1GTPase propertiesMutantsModest activationH-RasMutationsUrinary tract cancer
2006
Karyopherin-mediated import of integral inner nuclear membrane proteins
King MC, Lusk C, Blobel G. Karyopherin-mediated import of integral inner nuclear membrane proteins. Nature 2006, 442: 1003-1007. PMID: 16929305, DOI: 10.1038/nature05075.Peer-Reviewed Original ResearchConceptsIntegral membrane proteinsInner nuclear membraneINM proteinsMembrane proteinsIntegral inner nuclear membrane proteinsInner nuclear membrane proteinNuclear pore complex proteinsNuclear membrane proteinsRan GTPase cycleBasic sequence motifsNuclear localization signalNuclear pore complexPore complex proteinsAppropriate cellular compartmentDiscrete sequence elementsINM targetingLocalization signalPore complexGTPase cycleNuclear transportSequence motifsCellular compartmentsComplex proteinsSequence elementsKaryopherin β1
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