2019
Disruption of mosGILT in Anopheles gambiae impairs ovarian development and Plasmodium infection
Yang J, Schleicher TR, Dong Y, Park HB, Lan J, Cresswell P, Crawford J, Dimopoulos G, Fikrig E. Disruption of mosGILT in Anopheles gambiae impairs ovarian development and Plasmodium infection. Journal Of Experimental Medicine 2019, 217: e20190682. PMID: 31658986, PMCID: PMC7037243, DOI: 10.1084/jem.20190682.Peer-Reviewed Original ResearchConceptsMutant mosquitoesOvarian developmentThioester-containing protein 1Rodent Plasmodium speciesMajor yolk proteinInducible lysosomal thiol reductaseAbility of sporozoitesExpression of vitellogeninLysosomal thiol reductaseAnopheles gambiae mosquitoesPlasmodium infectionMosquito immunityProtein 9Yolk proteinsThiol reductaseVertebrate hostsTraverse cellsMosquito factorsGambiae mosquitoesProtein 1Plasmodium speciesAnophelesMosquitoesMosaic mutationsParasite killingBiocatalytic Reversal of Advanced Glycation End Product Modification
Kim NY, Goddard TN, Sohn S, Spiegel DA, Crawford J. Biocatalytic Reversal of Advanced Glycation End Product Modification. ChemBioChem 2019, 20: 2402-2410. PMID: 31013547, PMCID: PMC6768434, DOI: 10.1002/cbic.201900158.Peer-Reviewed Original ResearchConceptsImproved catalytic propertiesCondensation of sugarsLysine structureStructural homology analysisCatalytic propertiesSite-directed mutagenesisLead catalystFree amino acid formAcid formEnzyme variantsMaillard reactionHomology analysisCausal agentAuthentic ligandMolecular levelAdvanced glycation end product modificationAmino acid formMnmCLack of toolsAdvanced glycation end productsCatalystPeptidomimeticsLigandsVariantsMoleculesStructure elucidation of colibactin and its DNA cross-links
Xue M, Kim CS, Healy AR, Wernke KM, Wang Z, Frischling MC, Shine EE, Wang W, Herzon SB, Crawford JM. Structure elucidation of colibactin and its DNA cross-links. Science 2019, 365 PMID: 31395743, PMCID: PMC6820679, DOI: 10.1126/science.aax2685.Peer-Reviewed Original ResearchConceptsColibactin-producing bacteriaCell biology dataColibactin gene clusterCombination of geneticsComplex secondary metabolitesGene clusterIsotope labelingSecondary metabolitesBiology dataColibactinHuman gutTandem mass spectrometryBacteriaPhysiological effectsMass spectrometryStructure elucidationGutGeneticsDNAEnzymeChemical synthesisEscherichiaElucidationMetabolitesLabeling
2017
Stilbene 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
2012
A Single Promoter Inversion Switches Photorhabdus Between Pathogenic and Mutualistic States
Somvanshi VS, Sloup RE, Crawford JM, Martin AR, Heidt AJ, Kim KS, Clardy J, Ciche TA. A Single Promoter Inversion Switches Photorhabdus Between Pathogenic and Mutualistic States. Science 2012, 337: 88-93. PMID: 22767929, PMCID: PMC4006969, DOI: 10.1126/science.1216641.Peer-Reviewed Original ResearchConceptsNematode intestinePromoter inversionVariable life historiesM-form cellsInsect infectionHost nematodesLife historyMicrobial populationsSecondary metabolitesAntibiotic toleranceIndividual cellsNematodesPhotorhabdusM formJuvenile offspringCellsPathogenic variantsFirst cellsDistinct formsMutualistsMutualismVariantsInsectsAvirulenceSmall cell variant
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