2010
[d4U]-Spacer-[HI-236] double-drug inhibitors of HIV-1 reverse-transcriptase
Younis Y, Hunter R, Muhanji C, Hale I, Singh R, Bailey C, Sullivan T, Anderson K. [d4U]-Spacer-[HI-236] double-drug inhibitors of HIV-1 reverse-transcriptase. Bioorganic & Medicinal Chemistry 2010, 18: 4661-4673. PMID: 20605472, PMCID: PMC2964380, DOI: 10.1016/j.bmc.2010.05.025.Peer-Reviewed Original Research
2003
Characterization of Novel Reverse Transcriptase and Other RNA-associated Catalytic Activities by Human DNA Polymerase γ IMPORTANCE IN MITOCHONDRIAL DNA REPLICATION*
Murakami E, Feng J, Lee H, Hanes J, Johnson K, Anderson K. Characterization of Novel Reverse Transcriptase and Other RNA-associated Catalytic Activities by Human DNA Polymerase γ IMPORTANCE IN MITOCHONDRIAL DNA REPLICATION*. Journal Of Biological Chemistry 2003, 278: 36403-36409. PMID: 12857740, DOI: 10.1074/jbc.m306236200.Peer-Reviewed Original ResearchConceptsMtDNA genomeMtDNA replicationPol gammaInitiation of mtDNA replicationRNA-primed DNA synthesisHuman mitochondrial DNA polymeraseMitochondrial DNA polymeraseReverse transcriptionDNA synthesis activityPhysiologically relevant ratesMitochondrial DNARibonucleotide incorporationProofreading activitySingle ribonucleotidesHeteroduplex intermediatesRibonucleotide triphosphatesRNA templateDNA primersDNA polymeraseReverse transcriptaseDNA excisionMtDNAAccessory subunitsDNA synthesisEnzymatic pathways
2002
The Kinetic Mechanism of the Human Bifunctional Enzyme ATIC (5-Amino-4-imidazolecarboxamide Ribonucleotide Transformylase/Inosine 5′-Monophosphate Cyclohydrolase) A SURPRISING LACK OF SUBSTRATE CHANNELING*
Bulock K, Beardsley G, Anderson K. The Kinetic Mechanism of the Human Bifunctional Enzyme ATIC (5-Amino-4-imidazolecarboxamide Ribonucleotide Transformylase/Inosine 5′-Monophosphate Cyclohydrolase) A SURPRISING LACK OF SUBSTRATE CHANNELING*. Journal Of Biological Chemistry 2002, 277: 22168-22174. PMID: 11948179, DOI: 10.1074/jbc.m111964200.Peer-Reviewed Original ResearchConceptsCyclohydrolase reactionProduction of inosine monophosphateRelease of tetrahydrofolateSteady-state kinetic techniquesStopped-flow absorbanceBifunctional enzymeActive siteBifunctional proteinSubstrate channelingInosine 5'-monophosphateCyclohydrolaseEnzymatic activityChemotherapeutic targetEnzyme reaction pathwayInosine monophosphateKinetic mechanismFormyltransferaseProteinEnzymeKinetic analysisPathwayKinetic advantageKinetic evidenceKinetic techniquesRibonucleotides
2000
Energetics of S-Adenosylmethionine Synthetase Catalysis †
McQueney M, Anderson K, Markham G. Energetics of S-Adenosylmethionine Synthetase Catalysis †. Biochemistry 2000, 39: 4443-4454. PMID: 10757994, DOI: 10.1021/bi992876s.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAmino Acid SequenceBinding SitesCatalysisComputer SimulationDiphosphatesEscherichia coliFluorescenceHydrolysisIsomerismKineticsLigandsMethionineMethionine AdenosyltransferaseOxygenOxygen IsotopesPhosphatesPolyphosphatesS-AdenosylmethionineSolventsThermodynamicsTitrimetryWaterConceptsFree energy profilesSubstrate bindingLoop movementEnergy profilesFormation of AdoMetS-adenosylmethionineChemical interconversion stepPre-steady-state kineticsS-adenosylmethionine synthetaseProduct releaseP(i) complexEquilibrium binding measurementsEnzyme-catalyzed reactionsAdoMet formationBiological alkylating agentsConcentration of substrateFormation reactionCrystallographic studiesEnzyme turnoverEquilibrium constantsCatalyze formationRate constantsInterconversion stepActive siteBinding energy
1999
Initiation of Minus-Strand DNA Synthesis by Human Immunodeficiency Virus Type 1 Reverse Transcriptase †
Vaccaro J, Singh H, Anderson K. Initiation of Minus-Strand DNA Synthesis by Human Immunodeficiency Virus Type 1 Reverse Transcriptase †. Biochemistry 1999, 38: 15978-15985. PMID: 10625465, DOI: 10.1021/bi990945x.Peer-Reviewed Original ResearchConceptsHIV-1 reverse transcriptaseDNA/DNA substratesReverse transcriptaseHuman immunodeficiency virus type 1 reverse transcriptaseType 1 reverse transcriptasePrimer-template substrateDNA synthesisMinus-strand DNA synthesisConcentrations of dCTPDNA/RNADeoxynucleotide incorporationMolecular mechanismsTranscriptaseSteady-state releaseInitiationHigh affinityRNAReleaseStrand DNA synthesisThe Catalytic Mechanism of EPSP Synthase Revisited †
Lewis J, Johnson K, Anderson K. The Catalytic Mechanism of EPSP Synthase Revisited †. Biochemistry 1999, 38: 7372-7379. PMID: 10353849, DOI: 10.1021/bi9830258.Peer-Reviewed Original ResearchMeSH Keywords3-Phosphoshikimate 1-CarboxyvinyltransferaseAlkyl and Aryl TransferasesAmino Acid SubstitutionBinding SitesCatalysisChromatography, High Pressure LiquidEscherichia coliFreezingKineticsMutagenesis, Site-DirectedNuclear Magnetic Resonance, BiomolecularPhosphoenolpyruvateProtonsSubstrate SpecificityConceptsEPSP synthaseEnzyme intermediateKinetic competenceSingle-turnover experimentsSubstrate to productSolid-state NMRSolid-state NMR studiesEnzyme assaysEnzyme reaction pathwaySDS-PAGECatalytic mechanismDegrees CSpeciesEnzymeIntermediate speciesNMR studiesSide productsCharacterized reaction productsSample preparationDisappearance of substrateSynthaseReaction productsFormation of productsBreakdown productsReaction pathways[6] Fundamental mechanisms of substrate channeling
Anderson K. [6] Fundamental mechanisms of substrate channeling. Methods In Enzymology 1999, 308: 111-145. PMID: 10507003, DOI: 10.1016/s0076-6879(99)08008-8.Peer-Reviewed Original ResearchAnimalsBinding SitesCarbamoyl-Phosphate Synthase (Ammonia)Citrate (si)-SynthaseDiffusionDimerizationGlycerophosphatesIndolesKineticsLeishmania majorMagnetic Resonance SpectroscopyMalate DehydrogenaseModels, MolecularMultienzyme ComplexesMutationPeptide SynthasesProtein ConformationSalmonella typhimuriumTetrahydrofolate DehydrogenaseThymidylate SynthaseTryptophan Synthase
1998
Mechanistic Studies Comparing the Incorporation of (+) and (−) Isomers of 3TCTP by HIV-1 Reverse Transcriptase †
Feng J, Anderson K. Mechanistic Studies Comparing the Incorporation of (+) and (−) Isomers of 3TCTP by HIV-1 Reverse Transcriptase †. Biochemistry 1998, 38: 55-63. PMID: 9890882, DOI: 10.1021/bi982340r.Peer-Reviewed Original ResearchSubstrate Channeling and Domain−Domain Interactions in Bifunctional Thymidylate Synthase−Dihydrofolate Reductase †
Liang P, Anderson K. Substrate Channeling and Domain−Domain Interactions in Bifunctional Thymidylate Synthase−Dihydrofolate Reductase †. Biochemistry 1998, 37: 12195-12205. PMID: 9724533, DOI: 10.1021/bi9803168.Peer-Reviewed Original ResearchConceptsDHFR active siteActive siteTS active siteCrystal structureTransient kinetic analysisEnzyme active siteBifunctional TS-DHFRProtein surfaceTS-DHFRKinetics of substrateReductase enzymeSingle polypeptide chainKinetic analysisDihydrofolateThymidylate synthasePolypeptide chainSubstrateEnzymeStructureDomain-domain interactionsSpecies of protozoaInteractionKineticsL. majorChainKinetic Reaction Scheme for the Dihydrofolate Reductase Domain of the Bifunctional Thymidylate Synthase−Dihydrofolate Reductase from Leishmania major †
Liang P, Anderson K. Kinetic Reaction Scheme for the Dihydrofolate Reductase Domain of the Bifunctional Thymidylate Synthase−Dihydrofolate Reductase from Leishmania major †. Biochemistry 1998, 37: 12206-12212. PMID: 9724534, DOI: 10.1021/bi9803170.Peer-Reviewed Original ResearchConceptsThymidylate synthase-dihydrofolate reductaseKinetic reaction schemeCatalytic activityDihydrofolate reductaseBifunctional enzymeReaction schemeBifunctional thymidylate synthase-dihydrofolate reductaseE. coli enzymeSynthase-dihydrofolate reductaseSteady-state turnoverDihydrofolate reductase domainState kinetic methodsSingle polypeptide chainEnzyme dihydrofolate reductaseSpecies of protozoaReaction pathwaysRelease of productsColi enzymeParasite Leishmania majorMonofunctional formsDihydrofolate reductase activityReductase domainConformational changesKinetic stepsPolypeptide chainStructure and Functional Relationships in Human pur H
Beardsley G, Rayl E, Gunn K, Moroson B, Seow H, Anderson K, Vergis J, Fleming K, Worland S, Condon B, Davies J. Structure and Functional Relationships in Human pur H. Advances In Experimental Medicine And Biology 1998, 431: 221-226. PMID: 9598063, DOI: 10.1007/978-1-4615-5381-6_43.Peer-Reviewed Original Research
1997
Pre-Steady-State Kinetic Analysis of the Trichodiene Synthase Reaction Pathway †
Cane D, Chiu H, Liang P, Anderson K. Pre-Steady-State Kinetic Analysis of the Trichodiene Synthase Reaction Pathway †. Biochemistry 1997, 36: 8332-8339. PMID: 9204880, DOI: 10.1021/bi963018o.Peer-Reviewed Original ResearchConceptsChemical catalysisReaction pathwaysRapid chemical quench methodsActive siteSteady-state catalytic rateSingle turnover reactionsRate constant kcatEnzyme active siteNerolidyl diphosphateDeuterium isotope effectSingle-turnover experimentsSingle turnover rateState kinetic analysisTurnover reactionsDetection limitCatalytic rateOverall reactionSteady-state releaseIsotope effectRate-limiting stepState kineticsCatalysisReactionQuench methodSynthase reaction
1996
HIV-1 Reverse Transcriptase Resistance to Nonnucleoside Inhibitors †
Spence R, Anderson K, Johnson K. HIV-1 Reverse Transcriptase Resistance to Nonnucleoside Inhibitors †. Biochemistry 1996, 35: 1054-1063. PMID: 8547241, DOI: 10.1021/bi952058+.Peer-Reviewed Original ResearchConceptsMutant enzymesPre-steady-state techniquesSingle nucleotide incorporationWild-type complexMaximum incorporation rateNucleotide incorporationEnzyme complexDuplex DNAAffinity 2Cysteine mutationsTwo-step bindingWild-typeConformational changesDecreased affinityEnzymePresence of nevirapineInhibitor resistanceMutationsIncorporation rateY181C mutationWild-type RTReverse transcriptaseHIV-1NevirapineY181C
1995
Kinetic Characterization of Channel Impaired Mutants of Tryptophan Synthase (∗)
Anderson K, Kim A, Quillen J, Sayers E, Yang X, Miles E. Kinetic Characterization of Channel Impaired Mutants of Tryptophan Synthase (∗). Journal Of Biological Chemistry 1995, 270: 29936-29944. PMID: 8530393, DOI: 10.1074/jbc.270.50.29936.Peer-Reviewed Original ResearchBinding SitesCarbon RadioisotopesGlycerophosphatesIndolesKineticsMacromolecular SubstancesMathematicsModels, TheoreticalMutagenesis, Site-DirectedPoint MutationProtein ConformationRadioisotope Dilution TechniqueRecombinant ProteinsSalmonella typhimuriumSerineStructure-Activity RelationshipTryptophan SynthaseExpression of Human Cyclophilin‐40 and the Effect of the His141→Trp Mutation on Catalysis and Cyclosporin A Binding
Hoffmann K, Kakalis L, Anderson K, Armitage I, Handschumacher R. Expression of Human Cyclophilin‐40 and the Effect of the His141→Trp Mutation on Catalysis and Cyclosporin A Binding. The FEBS Journal 1995, 229: 188-193. PMID: 7744028, DOI: 10.1111/j.1432-1033.1995.0188l.x.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid IsomerasesBase SequenceBinding SitesCarrier ProteinsCyclophilin DCyclophilinsCyclosporineEnzyme ActivationEscherichia coliHumansMagnetic Resonance SpectroscopyModels, MolecularMolecular Sequence DataMutagenesis, Site-DirectedPeptidylprolyl IsomeraseProtein BindingRecombinant ProteinsConceptsCyP-40Isomerase activityPeptidyl-prolyl cis-trans isomerase activityHuman cyclophilin-40PGEX-3X expression vectorSite-directed mutagenesisMutant proteinsCyclophilin 40Intrinsic isomerase activityNMR difference spectroscopySuccinyl-AlaExpression vectorHistidine residuesEscherichia coliTryptophan residuesProteinCyclophilinMolecular modellingAla-ProResiduesGel filtrationWeak affinityBindingHigh affinityAffinity matrixCrystallization and preliminary X‐ray investigation of the recombinant Trypanosoma brucei rhodesiense calmodulin
El‐Sayed N, Patton C, Harkins P, Fox R, Anderson K. Crystallization and preliminary X‐ray investigation of the recombinant Trypanosoma brucei rhodesiense calmodulin. Proteins Structure Function And Bioinformatics 1995, 21: 354-357. PMID: 7567957, DOI: 10.1002/prot.340210409.Peer-Reviewed Original ResearchConceptsPreliminary X-ray investigationUnit cell dimensionsMolecular replacement methodX-ray investigationsSpace groupAsymmetric unitCrystal structureCell dimensionsRecombinant calmodulinMolecular massCrystalUnit cellTrypanosoma brucei rhodesienseVapor diffusionReplacement methodM cacodylate bufferCalmodulinStructureMechanism of Inhibition of HIV-1 Reverse Transcriptase by Nonnucleoside Inhibitors
Spence R, Kati W, Anderson K, Johnson K. Mechanism of Inhibition of HIV-1 Reverse Transcriptase by Nonnucleoside Inhibitors. Science 1995, 267: 988-993. PMID: 7532321, PMCID: PMC7526747, DOI: 10.1126/science.7532321.Peer-Reviewed Original ResearchConceptsActive site catalytic residuesPre-steady-state kinetic analysisNucleotide-induced conformational changesInterfere with nucleotide bindingPre-steady-state burstEnzyme-DNA complexPre-steady-stateReverse transcriptasePresence of saturating concentrationsCatalytic residuesNucleotide bindingNucleoside triphosphatesDNA polymerizationNucleotide analogsHydrophobic pocketMechanism of inhibitionNonnucleoside inhibitorsConformational changesNoncompetitive inhibitorInhibition of HIV-1 reverse transcriptaseKinetic analysisHIV-1 reverse transcriptaseSaturating concentrationsTranscriptaseInhibitors
1994
Detection and characterization of a phospholactoyl-enzyme adduct in the reaction catalyzed by UDP-N-acetylglucosamine enolpyruvoyl transferase, MurZ.
Brown E, Marquardt J, Lee J, Walsh C, Anderson K. Detection and characterization of a phospholactoyl-enzyme adduct in the reaction catalyzed by UDP-N-acetylglucosamine enolpyruvoyl transferase, MurZ. Biochemistry 1994, 33: 10638-45. PMID: 8075064, DOI: 10.1021/bi00201a010.Peer-Reviewed Original ResearchConceptsUDP-N-acetylglucosamineUDP-GlcNAcAbsence of UDP-GlcNAcChemical quench analysisPresence of UDP-GlcNAcSingle-turnover conditionsBinding constantsPeptidoglycan biosynthesisSolution NMRC-2Enzyme nucleophilePeptide of molecular weightStoichiometric labelingConsistent with catalysisRemoval of small moleculesE. coliAdductsSmall moleculesMurZEnzyme adductNon-covalentlySDS-PAGEM ureaLabeled peptidesEnzyme
1992
Mechanism and fidelity of HIV reverse transcriptase.
Kati W, Johnson K, Jerva L, Anderson K. Mechanism and fidelity of HIV reverse transcriptase. Journal Of Biological Chemistry 1992, 267: 25988-25997. PMID: 1281479, DOI: 10.1016/s0021-9258(18)35706-5.Peer-Reviewed Original ResearchMeSH KeywordsBase SequenceBinding SitesDeoxyribonucleotidesDNAEscherichia coliHIV Reverse TranscriptaseHIV-1KineticsModels, BiologicalMolecular Sequence DataNucleic Acid HeteroduplexesOligodeoxyribonucleotidesOligoribonucleotidesRecombinant ProteinsRNARNA-Directed DNA PolymeraseSubstrate SpecificityTemplates, GeneticConceptsRNA templateRNA/DNA heteroduplexesRNA cleavageDuplex DNAPre-steady state burstRate of DNA polymerizationDNA-dependent polymerasesRNA cleavage productsBinding of dNTPSingle nucleotide incorporationRibonuclease domainRNA-dependentVirus reverse transcriptasePublished crystal structureNucleotide incorporationNucleoside triphosphatesHuman immunodeficiency virus reverse transcriptaseDNTP complexDissociation of DNADNA polymerizationReverse transcriptaseDATPHeteroduplexCleavage productsRNA
1991
Serine modulates substrate channeling in tryptophan synthase. A novel intersubunit triggering mechanism
Anderson K, Miles E, Johnson K. Serine modulates substrate channeling in tryptophan synthase. A novel intersubunit triggering mechanism. Journal Of Biological Chemistry 1991, 266: 8020-8033. PMID: 1902468, DOI: 10.1016/s0021-9258(18)92934-0.Peer-Reviewed Original ResearchConceptsIndole-3-glycerol phosphateTryptophan synthaseProtein conformationAlpha 2 beta 2 complexReaction of serineAbsence of serineBeta siteFormation of tryptophanAlpha siteSteady-state turnoverActive siteAccumulation of indoleAlpha reactionSubstitution of cysteineSubstrate channelingBeta reactionBeta subunitMetabolic intermediatesSerineAlpha subunitQuench-flowProtein fluorescenceTurnover experimentsProteinTryptophan release