2024
Iguratimod, an allosteric inhibitor of macrophage migration inhibitory factor (MIF), prevents mortality and oxidative stress in a murine model of acetaminophen overdose
Bloom J, Pantouris G, He M, Aljabari B, Mishra L, Manjula R, Parkins A, Lolis E, Al-Abed Y. Iguratimod, an allosteric inhibitor of macrophage migration inhibitory factor (MIF), prevents mortality and oxidative stress in a murine model of acetaminophen overdose. Molecular Medicine 2024, 30: 43. PMID: 38539088, PMCID: PMC10976746, DOI: 10.1186/s10020-024-00803-0.Peer-Reviewed Original ResearchConceptsMode of inhibitionAllosteric inhibitorsActive site pocketMigration inhibitory factorSite pocketInhibitory factorProtein crystallographyTautomerase active siteOxidative stressT-614Murine modelDrug modePleiotropic cytokineNon-competitive type of inhibitionAPAP overdoseActive siteMacrophage migration inhibitory factorInhibition constantType of inhibitionInhibitor of macrophage migration inhibitory factorKinetic analysisBackgroundMacrophage migration inhibitory factorAcetaminophen overdoseIn vivo experimentsMultiple small molecule inhibitors
1999
Crystallographic Studies of Phosphonate-Based α-Reaction Transition-State Analogues Complexed to Tryptophan Synthase † , ‡
Sachpatzidis A, Dealwis C, Lubetsky J, Liang P, Anderson K, Lolis E. Crystallographic Studies of Phosphonate-Based α-Reaction Transition-State Analogues Complexed to Tryptophan Synthase † , ‡. Biochemistry 1999, 38: 12665-12674. PMID: 10504236, DOI: 10.1021/bi9907734.Peer-Reviewed Original ResearchConceptsTransition stateShort hydrogen bondsTryptophan synthaseHigh conformational flexibilityTetrahedral transition stateTransition state analogueMechanism of catalysisEnzyme-inhibitor complexStructure-based approachPhosphonate oxygenIndole-3-glycerol phosphateHydroxyl oxygenHydrogen bondsSulfur atomsActive siteC3 atomC2 atomCrystal structureConformational flexibilityCrystallographic studiesInhibitor bindingConformation changeAtomsNew herbicidesGlu-49
1998
Direct link between cytokine activity and a catalytic site for macrophage migration inhibitory factor
Swope M, Sun H, Blake P, Lolis E. Direct link between cytokine activity and a catalytic site for macrophage migration inhibitory factor. The EMBO Journal 1998, 17: 3534-3541. PMID: 9649424, PMCID: PMC1170690, DOI: 10.1093/emboj/17.13.3534.Peer-Reviewed Original ResearchConceptsN-terminal prolineN-terminal regionStructure-based inhibitorsMultiple sequence alignmentThree-dimensional structureInvariant residuesEntire polypeptideMicrobial enzymesCatalytic basePro-1Sequence alignmentMIF homologuesCytokine activityHuman macrophage migration inhibitory factorCatalytic siteProlineInhibitory factorHomologuesUnderlying biological activityP-hydroxyphenylpyruvateProteinMacrophage migration inhibitory factorActive siteBiological activity
1994
Crystal structure of the K12M/G15A triosephosphate isomerase double mutant and electrostatic analysis of the active site.
Joseph-McCarthy D, Lolis E, Komives E, Petsko G. Crystal structure of the K12M/G15A triosephosphate isomerase double mutant and electrostatic analysis of the active site. Biochemistry 1994, 33: 2815-23. PMID: 8130194, DOI: 10.1021/bi00176a010.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceBase SequenceBinding SitesCrystallizationCrystallography, X-RayDNA PrimersLigandsModels, MolecularMolecular Sequence DataMutagenesis, Site-DirectedPoint MutationProtein FoldingProtein Structure, SecondaryRecombinant ProteinsSaccharomyces cerevisiaeTriose-Phosphate IsomeraseX-Ray DiffractionConceptsMutant enzymesSubstrate-binding loopActive-site LysLys-12Wild-type enzymeMet side chainsActive siteEnzyme-inhibitor complexThree-dimensional structureMutant structuresWild typeTriosephosphate isomeraseDianionic substrateEnzymeSame crystal formCrystal structureMET mutationsSide chainsIsomeraseSitesCrystal formsMutationsPhosphoglycolohydroxamateMethionine
1990
Structure of yeast triosephosphate isomerase at 1.9-A resolution.
Lolis E, Alber T, Davenport R, Rose D, Hartman F, Petsko G. Structure of yeast triosephosphate isomerase at 1.9-A resolution. Biochemistry 1990, 29: 6609-18. PMID: 2204417, DOI: 10.1021/bi00480a009.Peer-Reviewed Original ResearchConceptsHydrogen bonding interactionsYeast triosephosphate isomeraseActive site structureNon-hydrogen atomsWater moleculesActive siteActive site residuesDrug designGlu-165Triosephosphate isomeraseSite structureCatalytic baseCrystal contactsSite residuesR factorTIM structuresFlexible loopLys-12Polypeptide chainStructureSubunit interfaceCarboxylateMonomersHydroxylFirst timeCrystallographic analysis of the complex between triosephosphate isomerase and 2-phosphoglycolate at 2.5-A resolution: implications for catalysis.
Lolis E, Petsko G. Crystallographic analysis of the complex between triosephosphate isomerase and 2-phosphoglycolate at 2.5-A resolution: implications for catalysis. Biochemistry 1990, 29: 6619-25. PMID: 2204418, DOI: 10.1021/bi00480a010.Peer-Reviewed Original ResearchConceptsHydrogen bondsSide chainsGlu-165Triosephosphate isomeraseLatter hydrogen bondTransition state analogueFinal R factorEnzyme-inhibitor complexSpectroscopic resultsActive siteConformational changesCrystallographic analysisLoop movesPhosphoglycolic acidIsomeraseUnbound formCatalysisR factorBondsEnzymeComplexesStructural termsAtomic modelBindingChain