2017
ClbS Is a Cyclopropane Hydrolase That Confers Colibactin Resistance
Tripathi P, Shine EE, Healy AR, Kim CS, Herzon SB, Bruner SD, Crawford JM. ClbS Is a Cyclopropane Hydrolase That Confers Colibactin Resistance. Journal Of The American Chemical Society 2017, 139: 17719-17722. PMID: 29112397, PMCID: PMC6202678, DOI: 10.1021/jacs.7b09971.Peer-Reviewed Original ResearchMeSH KeywordsBinding SitesCrystallography, X-RayCyclopropanesDrug ResistanceEscherichia coliHydrolasesMicrobial ViabilityPeptidesPolyketidesConceptsGene productsBiosynthetic gene clusterSpecific mechanistic roleMolecular functionsGene clusterResidue mutantsHost bacteriaCancer formationColorectal cancer formationEscherichia coliCommensal Escherichia coliColibactinMechanistic roleHydrolase activityPrecolibactinsX-ray structureMolecular-level viewShare similaritiesElectrophilic CyclopropanesBacterial viabilityBacteriaHydrolaseGenotoxic effectsMutantsBiosynthesisStructure and Functional Analysis of ClbQ, an Unusual Intermediate-Releasing Thioesterase from the Colibactin Biosynthetic Pathway
Guntaka NS, Healy AR, Crawford JM, Herzon SB, Bruner SD. Structure and Functional Analysis of ClbQ, an Unusual Intermediate-Releasing Thioesterase from the Colibactin Biosynthetic Pathway. ACS Chemical Biology 2017, 12: 2598-2608. PMID: 28846367, PMCID: PMC5830302, DOI: 10.1021/acschembio.7b00479.Peer-Reviewed Original ResearchConceptsColibactin gene clusterÅ crystal structurePolyketide secondary metabolitesAcyl-thioester substratesColibactin biosynthesisGene clusterBiosynthetic pathwayAtypical roleGene productsBiochemical characterizationFunctional analysisSecondary metabolitesGreater catalytic efficiencyCancer formationColorectal cancer formationHuman gutSpecific functionsNovel insightsCarrier proteinThioesteraseGenetic deletionClbQColibactinCatalytic efficiencyPathwayStilbene epoxidation and detoxification in a Photorhabdus luminescens-nematode symbiosis
Park HB, Sampathkumar P, Perez CE, Lee JH, Tran J, Bonanno JB, Hallem EA, Almo SC, Crawford JM. Stilbene epoxidation and detoxification in a Photorhabdus luminescens-nematode symbiosis. Journal Of Biological Chemistry 2017, 292: 6680-6694. PMID: 28246174, PMCID: PMC5399116, DOI: 10.1074/jbc.m116.762542.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnti-Infective AgentsBiological ProductsCatalysisChromatography, High Pressure LiquidCrystallography, X-RayDNA Mutational AnalysisEpoxy CompoundsGene DeletionHydrogen BondingHydrophobic and Hydrophilic InteractionsImmunosuppressive AgentsMagnetic Resonance SpectroscopyMolecular ConformationMutationPhotorhabdusProtein FoldingRhabditoideaStereoisomerismStilbenesSymbiosisConceptsFood signalsInsect infection modelFAD-dependent monooxygenasesFAD prosthetic groupOrphan proteinsInsect larvaeMutualistic relationshipEpoxidase geneNematode developmentCellular detoxificationBiological roleProsthetic groupIntracellular detoxificationAnimal infection modelsInfection modelBiochemical analysisChemical degradation studiesStructural viewNematodesDetoxificationNew insightsCompound 1Major componentNew stilbeneRecovery assays
2010
Structure and function of an iterative polyketide synthase thioesterase domain catalyzing Claisen cyclization in aflatoxin biosynthesis
Korman TP, Crawford JM, Labonte JW, Newman AG, Wong J, Townsend CA, Tsai SC. Structure and function of an iterative polyketide synthase thioesterase domain catalyzing Claisen cyclization in aflatoxin biosynthesis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 6246-6251. PMID: 20332208, PMCID: PMC2851968, DOI: 10.1073/pnas.0913531107.Peer-Reviewed Original ResearchConceptsPolyketide synthasesCrystal structureC bond formationPolyketide natural productsProduct release mechanismRing closure reactionAlpha/beta hydrolase foldSynthetic versatilitySynthetic potentialSubstrate-binding chamberIterative polyketide synthasesC cyclizationFatty acid synthasesBond formationClaisen cyclizationFirst mechanistic insightsProtein conformational changesNatural productsClosure reactionSubstrate positioningSide chainsBiosynthesis of aflatoxinSubstrate side chainDiverse architecturesPolyketide synthase A
2009
Structural basis for biosynthetic programming of fungal aromatic polyketide cyclization
Crawford JM, Korman TP, Labonte JW, Vagstad AL, Hill EA, Kamari-Bidkorpeh O, Tsai SC, Townsend CA. Structural basis for biosynthetic programming of fungal aromatic polyketide cyclization. Nature 2009, 461: 1139-1143. PMID: 19847268, PMCID: PMC2872118, DOI: 10.1038/nature08475.Peer-Reviewed Original ResearchConceptsProduct templateX-ray crystal structurePt domainsIntramolecular aldol cyclizationCo-crystal structureIterative polyketide synthaseBicyclic compoundsPolyketide cyclizationNatural productsCrystal structureAldol cyclizationDiverse structuresBiological activityBiosynthetic reactionsCyclizationPolyketide synthaseAflatoxin B1Structural basisStructureIntermediatesCompoundsReactionPotent hepatocarcinogen aflatoxin B1TemplateHepatocarcinogen aflatoxin B1
2006
New Images Evoke FAScinating Questions
Townsend CA, Crawford JM, Bililign T. New Images Evoke FAScinating Questions. Cell Chemical Biology 2006, 13: 349-351. PMID: 16632247, DOI: 10.1016/j.chembiol.2006.04.001.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCatalytic DomainCrystallography, X-RayFatty Acid SynthasesFungiModels, MolecularMolecular StructureProtein Structure, QuaternaryProtein Structure, Tertiary