1998
Structure of Human Methionine Aminopeptidase-2 Complexed with Fumagillin
Liu S, Widom J, Kemp C, Crews C, Clardy J. Structure of Human Methionine Aminopeptidase-2 Complexed with Fumagillin. Science 1998, 282: 1324-1327. PMID: 9812898, DOI: 10.1126/science.282.5392.1324.Peer-Reviewed Original ResearchConceptsStructure-based drug designMetAP-2Resolution crystal structureCovalent bondsMethionine aminopeptidase 2Active siteCrystal structurePolar interactionsDrug designThree-dimensional structureExtensive hydrophobicStructural basisMetAP-1Anticancer agentsNew blood vesselsFumagillin analoguesAdditional affinityReactive epoxidesMolecular targetsFumagillinStructureHydrophobicBondsLikely determinantsEpoxides
1997
The anti-angiogenic agent fumagillin covalently binds and inhibits the methionine aminopeptidase, MetAP-2
Sin N, Meng L, Wang M, Wen J, Bornmann W, Crews C. The anti-angiogenic agent fumagillin covalently binds and inhibits the methionine aminopeptidase, MetAP-2. Proceedings Of The National Academy Of Sciences Of The United States Of America 1997, 94: 6099-6103. PMID: 9177176, PMCID: PMC21008, DOI: 10.1073/pnas.94.12.6099.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAminopeptidasesAnimalsAntibiotics, AntineoplasticBinding SitesCattleCyclohexanesFatty Acids, UnsaturatedHumansKineticsMammalsMetalloendopeptidasesMethionyl AminopeptidasesMolecular Sequence DataNeovascularization, PathologicO-(Chloroacetylcarbamoyl)fumagillolSaccharomyces cerevisiaeSequence AlignmentSequence Homology, Amino AcidSesquiterpenesConceptsMethionine aminopeptidaseMetAP-1MetAP-2Mammalian proteinsBlood vessel formationVegetative growthTNP-470New blood vessel formationPotent biological activitiesMolecular modeProteinFungal metabolitesVessel formationAnimal model studiesAminopeptidaseAnti-angiogenic compoundsDetailed pharmacological studiesBiological activityImportant targetFumagillinClinical trialsSolid tumorsPharmacological studiesNatural productsSaccharomyces
1992
The Primary Structure of MEK, a Protein Kinase that Phosphorylates the ERK Gene Product
Crews C, Alessandrini A, Erikson R. The Primary Structure of MEK, a Protein Kinase that Phosphorylates the ERK Gene Product. Science 1992, 258: 478-480. PMID: 1411546, DOI: 10.1126/science.1411546.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBase SequenceCalcium-Calmodulin-Dependent Protein KinasesGene ExpressionMAP Kinase Kinase 1MiceMitogen-Activated Protein Kinase KinasesMolecular Sequence DataPhosphorylationProtein KinasesProtein Serine-Threonine KinasesProteinsProtein-Tyrosine KinasesRNA, MessengerSequence AlignmentConceptsExtracellular signal-regulated kinaseProtein kinaseMAP kinaseGene productsCritical protein kinaseSignal-regulated kinaseComplementary DNA sequenceMEK genesExtracellular signalsERK kinaseMultiple biochemical signalsDNA sequencesBiochemical signalsPrimary structureKinaseAmino acidsEnzymatic activityGenesMurine brainSequenceSchizosaccharomycesMEK1MEKThreonineProteinPurification of a murine protein-tyrosine/threonine kinase that phosphorylates and activates the Erk-1 gene product: relationship to the fission yeast byr1 gene product.
Crews CM, Erikson RL. Purification of a murine protein-tyrosine/threonine kinase that phosphorylates and activates the Erk-1 gene product: relationship to the fission yeast byr1 gene product. Proceedings Of The National Academy Of Sciences Of The United States Of America 1992, 89: 8205-8209. PMID: 1381507, PMCID: PMC49886, DOI: 10.1073/pnas.89.17.8205.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsEnzyme ActivationFungal ProteinsGenesMiceMitogen-Activated Protein Kinase 3Mitogen-Activated Protein KinasesMolecular Sequence DataPeptide FragmentsPhosphorylationPhosphoserinePhosphothreoninePhosphotyrosineProtein KinasesRecombinant ProteinsSequence AlignmentTyrosineConceptsGene productsProtein kinaseSerine/threonine phosphatase 2AMyelin basic protein kinaseProtein tyrosine phosphatase 1B.MAPK/ERK kinaseSignal transduction mechanismsPossible signal transduction mechanismsERK-1 proteinSte7 genePhosphatase 2AThreonine kinaseERK kinaseERK-1Tyrosine residuesSequence analysisKinaseTransduction mechanismsMEKTrypsin digestionProteinByr1PurificationGenesLesser extentErks: their fifteen minutes has arrived.
Crews CM, Alessandrini A, Erikson RL. Erks: their fifteen minutes has arrived. Molecular Cancer Research 1992, 3: 135-42. PMID: 1504018.Peer-Reviewed Original ResearchConceptsProtein kinaseCell cycleYeast cellsTyrosine kinase signalsERK protein kinasesSea star oocytesSpecific transcriptional factorsAmino acid residuesSpecific differentiation eventsG0-G1 transitionExtracellular signalsKinase signalsPhosphorylation signalsSignal transductionTranscriptional changesS6 kinaseRaf-1Differentiation eventsMitogenic signalsYeast enzymeGene productsMicrotubule reorganizationDownstream targetsTranscriptional factorsEGF receptor