2006
Structural characterization of autoinhibited c-Met kinase produced by coexpression in bacteria with phosphatase
Wang W, Marimuthu A, Tsai J, Kumar A, Krupka H, Zhang C, Powell B, Suzuki Y, Nguyen H, Tabrizizad M, Luu C, West B. Structural characterization of autoinhibited c-Met kinase produced by coexpression in bacteria with phosphatase. Proceedings Of The National Academy Of Sciences Of The United States Of America 2006, 103: 3563-3568. PMID: 16537444, PMCID: PMC1450123, DOI: 10.1073/pnas.0600048103.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceBase SequenceCrystallography, X-RayCSK Tyrosine-Protein KinaseDNAEscherichia coliGene ExpressionGenetic VectorsModels, MolecularMutationNeoplasmsPhosphotransferasesProtein Structure, TertiaryProtein Tyrosine Phosphatase, Non-Receptor Type 1Protein Tyrosine PhosphatasesProtein-Tyrosine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-ablProto-Oncogene Proteins c-metRecombinant ProteinsSrc-Family KinasesConceptsC-Met kinaseKinase active siteC-Abl kinaseTyrosine phosphataseUnphosphorylated formSmall molecule compoundsKinase domainProtein kinaseC-SrcActive sitePhosphorylated formC-AblKinaseIntricate networkBicistronic vectorEscherichia coliLarge familyNormal regulationX-ray crystallographyEnzyme activityConformation stateSelective inhibitorDifferent conformation statesPhosphataseInhibitors
2005
A family of phosphodiesterase inhibitors discovered by cocrystallography and scaffold-based drug design
Card GL, Blasdel L, England BP, Zhang C, Suzuki Y, Gillette S, Fong D, Ibrahim PN, Artis DR, Bollag G, Milburn MV, Kim SH, Schlessinger J, Zhang KY. A family of phosphodiesterase inhibitors discovered by cocrystallography and scaffold-based drug design. Nature Biotechnology 2005, 23: 201-207. PMID: 15685167, DOI: 10.1038/nbt1059.Peer-Reviewed Original ResearchConceptsDrug designX-ray crystallographyStructural analysisChemical synthesisDetailed structural analysisScaffold derivativesPyrazole derivativesChemical substitutionPotent PDE4 inhibitorsCarboxylic estersCellular processesDrug candidatesMolecular basisNew inhibitorsCyclic nucleotide phosphodiesterasesCocrystallographyLarge familyCompoundsNucleotide phosphodiesterasesDerivativesPhosphodiesterasesCrystallographyInhibitorsEfficient methodFamily
2004
Structural Basis for the Activity of Drugs that Inhibit Phosphodiesterases
Card GL, England BP, Suzuki Y, Fong D, Powell B, Lee B, Luu C, Tabrizizad M, Gillette S, Ibrahim PN, Artis DR, Bollag G, Milburn MV, Kim SH, Schlessinger J, Zhang KY. Structural Basis for the Activity of Drugs that Inhibit Phosphodiesterases. Structure 2004, 12: 2233-2247. PMID: 15576036, DOI: 10.1016/j.str.2004.10.004.Peer-Reviewed Original ResearchConceptsHigh-resolution crystal structuresInvariant glutamineHydrogen bondingCatalytic domainStructural basisStructural insightsIsoform-selective inhibitorsHydrolysis of cAMPHydrophobic residuesInhibitor bindingActive siteCrystal structureCocrystal structureHydrophobic clampLarge familyDifferent inhibitorsPhosphodiesterasesVariety of diseasesSelective PDE inhibitorsInhibitorsActivity of drugsPDE inhibitorsBondingEnzymeResidues