2023
Design, synthesis, and biological testing of biphenylmethyloxazole inhibitors targeting HIV-1 reverse transcriptase
Carter Z, Hollander K, Spasov K, Anderson K, Jorgensen W. Design, synthesis, and biological testing of biphenylmethyloxazole inhibitors targeting HIV-1 reverse transcriptase. Bioorganic & Medicinal Chemistry Letters 2023, 84: 129216. PMID: 36871704, PMCID: PMC10278203, DOI: 10.1016/j.bmcl.2023.129216.Peer-Reviewed Original ResearchMeSH KeywordsAnti-HIV AgentsDrug DesignHIV Reverse TranscriptaseHIV-1Models, MolecularReverse Transcriptase InhibitorsStructure-Activity Relationship
2012
Active site residues critical for flavin binding and 5,6‐dimethylbenzimidazole biosynthesis in the flavin destructase enzyme BluB
Yu T, Mok K, Kennedy K, Valton J, Anderson K, Walker G, Taga M. Active site residues critical for flavin binding and 5,6‐dimethylbenzimidazole biosynthesis in the flavin destructase enzyme BluB. Protein Science 2012, 21: 839-849. PMID: 22528544, PMCID: PMC3403419, DOI: 10.1002/pro.2068.Peer-Reviewed Original ResearchConceptsConserved residuesFlavin mononucleotideReduced catalytic functionPurified mutant proteinsBacterium Sinorhizobium melilotiActive site residuesReduced flavin mononucleotideFlavin isoalloxazine ringCatalytic residuesMutant proteinsFlavin bindingDMB synthesisStructure-function relationshipsActive siteEnzyme familyGenetic screeningSite residuesMutant formsLower axial ligandBound flavinCatalytic functionMutantsEnzyme assaysIsoalloxazine ringBluB
2010
mip1 containing mutations associated with mitochondrial disease causes mutagenesis and depletion of mtDNA in Saccharomyces cerevisiae
Stumpf J, Bailey C, Spell D, Stillwagon M, Anderson K, Copeland W. mip1 containing mutations associated with mitochondrial disease causes mutagenesis and depletion of mtDNA in Saccharomyces cerevisiae. Human Molecular Genetics 2010, 19: 2123-2133. PMID: 20185557, PMCID: PMC2865372, DOI: 10.1093/hmg/ddq089.Peer-Reviewed Original ResearchConceptsMitochondrial dysfunctionHuman pol gammaSaccharomyces cerevisiae orthologAssociated with mitochondrial diseasesDecreased polymerase activityAtaxia-neuropathy syndromeDepletion of mtDNADNA polymerase gammaDisease-associated mutationsMutations in vivoIncreased nucleotide poolOrthologous human mutationMtDNA replication defectsMtDNA mutagenesisMtDNA replicationProgressive external ophthalmoplegiaSaccharomyces cerevisiaeMutant strainMutant enzymesPol gammaHuman orthologPolymerase gammaConserved regionMtDNA depletionMtDNA
2006
Developing novel nonnucleoside HIV-1 reverse transcriptase inhibitors: beyond the butterfly.
Basavapathruni A, Anderson K. Developing novel nonnucleoside HIV-1 reverse transcriptase inhibitors: beyond the butterfly. Current Pharmaceutical Design 2006, 12: 1857-65. PMID: 16724952, DOI: 10.2174/138161206776873617.Peer-Reviewed Original ResearchConceptsNonnucleoside reverse transcriptase inhibitorsReverse transcriptase inhibitorsTranscriptase inhibitorsHuman immunodeficiency virus type 1 infectionResistance to nonnucleoside reverse transcriptase inhibitorsTreatment of human immunodeficiency virus type 1 infectionType 1 infectionFood and Drug AdministrationU.S. Food and Drug AdministrationCombination therapyDevelopment of resistanceMechanism of actionHIV-1 reverse transcriptase inhibitorsDrug AdministrationNonnucleosideNonnucleoside HIV-1 reverse transcriptase inhibitorNonnucleoside inhibitorsFeatures of inhibitionPotential new inhibitorsInhibitorsAmino acid substitutionsBiochemical featuresMolecular mechanismsNew inhibitorsAcid substitutions
2002
Mechanistic Characterization of Toxoplasma gondiiThymidylate Synthase (TS-DHFR)-Dihydrofolate Reductase EVIDENCE FOR A TS INTERMEDIATE AND TS HALF-SITES REACTIVITY*
Johnson E, Hinz W, Atreya C, Maley F, Anderson K. Mechanistic Characterization of Toxoplasma gondiiThymidylate Synthase (TS-DHFR)-Dihydrofolate Reductase EVIDENCE FOR A TS INTERMEDIATE AND TS HALF-SITES REACTIVITY*. Journal Of Biological Chemistry 2002, 277: 43126-43136. PMID: 12192007, DOI: 10.1074/jbc.m206523200.Peer-Reviewed Original Research
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 ResearchMeSH KeywordsCrystallography, X-RayEnzyme InhibitorsHydrogen BondingModels, MolecularOrganophosphonatesTryptophan SynthaseConceptsTransition 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[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 ResearchLoop Closure and Intersubunit Communication in Tryptophan Synthase † , ‡
Schneider T, Gerhardt E, Lee M, Liang P, Anderson K, Schlichting I. Loop Closure and Intersubunit Communication in Tryptophan Synthase † , ‡. Biochemistry 1998, 37: 5394-5406. PMID: 9548921, DOI: 10.1021/bi9728957.Peer-Reviewed Original ResearchConceptsBeta-active siteMechanism of allosteric activationAlpha-active siteAlpha subunitTryptophan synthase alpha2beta2 complexPyridoxal phosphateCofactor pyridoxal phosphatePresence of serineSalmonella typhimuriumIntersubunit communicationTryptophan synthaseAllosteric activationAlpha2beta2 complexAllosteric propertiesAlpha-reactionBeta-reactionBeta subunitStructural basisAminoacrylate intermediateAminoacrylatePathwayBindingSitesTryptophanSerineStructure 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
1996
Surface point mutations that significantly alter the structure and stability of a protein's denatured state
Smith C, Bu Z, Engelman D, Regan L, Anderson K, Sturtevant J. Surface point mutations that significantly alter the structure and stability of a protein's denatured state. Protein Science 1996, 5: 2009-2019. PMID: 8897601, PMCID: PMC2143264, DOI: 10.1002/pro.5560051007.Peer-Reviewed Original ResearchConceptsPoint mutationsDenatured stateStopped-flow fluorescenceDenaturant concentrationSolvent-exposed sitesStreptococcal protein GMutantsG mutantTertiary structureGuHCl denaturationEquilibrium intermediatesPosition 53B1 domainProteinCircular dichroismMutationsProtein GGuanidine hydrochlorideSmall-angle X-ray scatteringStructural implicationsX-ray scatteringFluorescenceThrRadius of gyrationDenaturantsIntersubunit Communication in Tryptophan Synthase by Carbon-13 and Fluorine-19 REDOR NMR †
McDowell L, Lee M, McKay R, Anderson K, Schaefer J. Intersubunit Communication in Tryptophan Synthase by Carbon-13 and Fluorine-19 REDOR NMR †. Biochemistry 1996, 35: 3328-3334. PMID: 8605170, DOI: 10.1021/bi9518297.Peer-Reviewed Original ResearchConceptsProton dipolar decouplingMagic angle spinningLocal electric field gradientsElectric field gradientIsotropic shiftsLigand bindingChemical shiftsNMR spectraConformational gatingEnzyme tryptophan synthaseBeta subunitCarbon-13Dipolar decouplingTryptophan synthaseMother liquorResolved linesConformational rearrangementsBinding of serineNMRLigandField gradientEnzyme complexIntersubunit communicationTyrosine residuesSubunit
1995
Expression 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 matrix