2017
Understanding the molecular mechanism of substrate channeling and domain communication in protozoal bifunctional TS-DHFR
Anderson K. Understanding the molecular mechanism of substrate channeling and domain communication in protozoal bifunctional TS-DHFR. Protein Engineering Design And Selection 2017, 30: 253-261. PMID: 28338744, PMCID: PMC6438133, DOI: 10.1093/protein/gzx004.Peer-Reviewed Original ResearchConceptsBifunctional thymidylate synthase-dihydrofolate reductaseThymidylate synthase-dihydrofolate reductaseSubstrate channelingDihydrofolate reductaseN-terminal amino acid extensionAmino acid extensionDihydrofolate reductase domainThymidylate synthaseFolate metabolizing enzymesAcid extensionMonofunctional formsPolypeptide chainMutation analysisMolecular mechanismsMetabolic enzymesParasitic protozoaDNA synthesisFunctional regionsInhibitor designSpeciesEnzymeStructural similarityStructural studiesEfficient catalysisLeishmania major
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
2001
Y265H Mutator Mutant of DNA Polymerase β PROPER GEOMETRIC ALIGNMENT IS CRITICAL FOR FIDELITY*
Shah A, Li S, Anderson K, Sweasy J. Y265H Mutator Mutant of DNA Polymerase β PROPER GEOMETRIC ALIGNMENT IS CRITICAL FOR FIDELITY*. Journal Of Biological Chemistry 2001, 276: 10824-10831. PMID: 11154692, DOI: 10.1074/jbc.m008680200.Peer-Reviewed Original ResearchConceptsDNA polymerase betaPolymerase betaVivo genetic screenWild-type proteinWild-type enzymeActive site residuesGenetic screenTyr-265Mutant proteinsMutator mutantsPolymerase structureProper geometric alignmentSite residuesProtein conformationNucleotidyl transferForward mutationDNA polymerasePolymerase fidelityDNTP substratesDNA synthesisProteinDeoxynucleoside triphosphatesFirst evidenceTemplate A.Enzyme
2000
Mechanism of Inhibition of the Human Immunodeficiency Virus Type 1 Reverse Transcriptase by d4TTP: an Equivalent Incorporation Efficiency Relative to the Natural Substrate dTTP
Vaccaro J, Parnell K, Terezakis S, Anderson K. Mechanism of Inhibition of the Human Immunodeficiency Virus Type 1 Reverse Transcriptase by d4TTP: an Equivalent Incorporation Efficiency Relative to the Natural Substrate dTTP. Antimicrobial Agents And Chemotherapy 2000, 44: 217-221. PMID: 10602755, PMCID: PMC89660, DOI: 10.1128/aac.44.1.217-221.2000.Peer-Reviewed Original ResearchConceptsHIV-1HIV-1 RTHuman immunodeficiency virus type 1Immunodeficiency virus type 1Target human immunodeficiency virus type 1Inhibition of HIV-1 RTNatural substrateVirus type 1Pre-steady-state kinetic analysisNucleoside analogue inhibitorsDNA synthesisRNA-dependent DNA synthesisAIDS patientsPrimer-template complexHuman immunodeficiency virus type 1 reverse transcriptaseNucleoside triphosphate analoguesType 1Mechanism of inhibitionD4TTPIncorporation efficiencyDTTPDNATriphosphate analoguesAnalogue inhibitorsInhibition
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 synthesisMechanistic studies show that (−)‐FTC‐TP is a better inhibitor of HIV‐1 reverse transcriptase than 3TC‐TP
Feng J, Shi J, Schinazi R, Anderson K. Mechanistic studies show that (−)‐FTC‐TP is a better inhibitor of HIV‐1 reverse transcriptase than 3TC‐TP. The FASEB Journal 1999, 13: 1511-1517. PMID: 10463941, DOI: 10.1096/fasebj.13.12.1511.Peer-Reviewed Original ResearchConceptsHIV-1 reverse transcriptaseFTC-TPClinical trialsReverse transcriptaseOngoing clinical trialsTreatment of AIDSAntiretroviral activityClinical potencyViral replicationBeta 2Triphosphate formNucleoside inhibitorsDifferential potencyRNA-dependent DNA synthesisEnhanced potencyTrialsPotencyMolecular mechanismsMechanistic studiesDNA synthesisInhibitorsTranscriptaseFTCMechanistic Studies Examining the Efficiency and Fidelity of DNA Synthesis by the 3TC-Resistant Mutant (184V) of HIV-1 Reverse Transcriptase †
Feng J, Anderson K. Mechanistic Studies Examining the Efficiency and Fidelity of DNA Synthesis by the 3TC-Resistant Mutant (184V) of HIV-1 Reverse Transcriptase †. Biochemistry 1999, 38: 9440-9448. PMID: 10413520, DOI: 10.1021/bi990709m.Peer-Reviewed Original ResearchConceptsHIV-1 reverse transcriptaseM184V RTHIV-1 virusWild-type HIV-1 reverse transcriptaseReverse transcriptaseDNA-dependent DNA polymerizationStrong antiviral effectRNA-dependent DNA polymerizationCombination therapyAntiviral effectMethionine 184Mutant reverse transcriptaseMutant HIV-1 reverse transcriptaseRT fidelityCorresponding DNA templateSingle amino acid substitutionMolecular mechanismsAmino acid substitutionsVirusDNA synthesisTranscriptaseAcid substitutionsHigh levelsClinicTherapy