2018
Crystallographic evidence for two‐metal‐ion catalysis in human pol η
Wang J, Smithline ZB. Crystallographic evidence for two‐metal‐ion catalysis in human pol η. Protein Science 2018, 28: 439-447. PMID: 30368948, PMCID: PMC6319759, DOI: 10.1002/pro.3541.Peer-Reviewed Original ResearchMeSH KeywordsBinding SitesCatalysisCrystallography, X-RayDNA-Directed DNA PolymeraseHumansMagnesiumModels, MolecularConceptsMetal ionsProduct pyrophosphateChemical reactionsTwo-metal-ion catalysisTwo-metal-ion catalytic mechanismThird metal ionPhosphoryl transfer reactionsTransfer reactionsCrystallographic dataCatalytic mechanismCrystal structureCrystallographic evidenceHuman Pol ηMeal ionsIonsHuman polymerase ηCatalysisReactionComplexesSubPyrophosphateBindingProductsDNA polymeraseCrystals
2016
Different Divalent Cations Alter the Kinetics and Fidelity of DNA Polymerases*
Vashishtha AK, Wang J, Konigsberg WH. Different Divalent Cations Alter the Kinetics and Fidelity of DNA Polymerases*. Journal Of Biological Chemistry 2016, 291: 20869-20875. PMID: 27462081, PMCID: PMC5076500, DOI: 10.1074/jbc.r116.742494.Peer-Reviewed Original ResearchConceptsMetal ionsWater moleculesTransfer reactionsDifferent divalent cationsOctahedral coordination geometryB metal ionsThird metal ionDifferent metal ionsAttacking water moleculeDivalent metal ionsNucleotidyl transfer reactionPhosphoryl transfer reactionsNon-bridging oxygen atomsOctahedral complexesCoordination geometryCarboxyl oxygenDivalent cationsOxygen atomsSixth ligandHydroxyl groupsTransition stateEffective nucleophilePhosphorous atomsIonsB-site
2012
DNA Mismatch Synthesis Complexes Provide Insights into Base Selectivity of a B Family DNA Polymerase
Xia S, Wang J, Konigsberg WH. DNA Mismatch Synthesis Complexes Provide Insights into Base Selectivity of a B Family DNA Polymerase. Journal Of The American Chemical Society 2012, 135: 193-202. PMID: 23214497, PMCID: PMC3760218, DOI: 10.1021/ja3079048.Peer-Reviewed Original ResearchContribution of Partial Charge Interactions and Base Stacking to the Efficiency of Primer Extension at and beyond Abasic Sites in DNA
Xia S, Vashishtha A, Bulkley D, Eom SH, Wang J, Konigsberg WH. Contribution of Partial Charge Interactions and Base Stacking to the Efficiency of Primer Extension at and beyond Abasic Sites in DNA. Biochemistry 2012, 51: 4922-4931. PMID: 22630605, PMCID: PMC3426629, DOI: 10.1021/bi300296q.Peer-Reviewed Original ResearchUsing a Fluorescent Cytosine Analogue tCo To Probe the Effect of the Y567 to Ala Substitution on the Preinsertion Steps of dNMP Incorporation by RB69 DNA Polymerase
Xia S, Beckman J, Wang J, Konigsberg WH. Using a Fluorescent Cytosine Analogue tCo To Probe the Effect of the Y567 to Ala Substitution on the Preinsertion Steps of dNMP Incorporation by RB69 DNA Polymerase. Biochemistry 2012, 51: 4609-4617. PMID: 22616982, PMCID: PMC3437246, DOI: 10.1021/bi300241m.Peer-Reviewed Original ResearchProbing Minor Groove Hydrogen Bonding Interactions between RB69 DNA Polymerase and DNA
Xia S, Christian TD, Wang J, Konigsberg WH. Probing Minor Groove Hydrogen Bonding Interactions between RB69 DNA Polymerase and DNA. Biochemistry 2012, 51: 4343-4353. PMID: 22571765, PMCID: PMC3374494, DOI: 10.1021/bi300416z.Peer-Reviewed Original ResearchStructural Basis for Differential Insertion Kinetics of dNMPs Opposite a Difluorotoluene Nucleotide Residue
Xia S, Eom SH, Konigsberg WH, Wang J. Structural Basis for Differential Insertion Kinetics of dNMPs Opposite a Difluorotoluene Nucleotide Residue. Biochemistry 2012, 51: 1476-1485. PMID: 22304682, PMCID: PMC3292180, DOI: 10.1021/bi2016487.Peer-Reviewed Original ResearchBidentate and tridentate metal‐ion coordination states within ternary complexes of RB69 DNA polymerase
Xia S, Eom SH, Konigsberg WH, Wang J. Bidentate and tridentate metal‐ion coordination states within ternary complexes of RB69 DNA polymerase. Protein Science 2012, 21: 447-451. PMID: 22238207, PMCID: PMC3375444, DOI: 10.1002/pro.2026.Peer-Reviewed Original ResearchMeSH KeywordsCalciumCations, DivalentCrystallography, X-RayDeoxyribonucleotidesDNA-Directed DNA PolymeraseMagnesiumMetalsModels, MolecularMolecular ConformationProtein ConformationViral ProteinsConceptsCoordination complexesMetal ionsCoordination stateSecond metal ionMetal ion coordinationDivalent metal ionsTernary complexTridentate coordinationBond formationPhosphorus atomActive siteRelevant conformationsStructural studiesSelectivity mechanismIonsTriphosphate tailComplexesRB69 DNA polymeraseÅ resolutionBase selectivityGround stateSubstrate alignmentPolymerase active siteCatalysisCoordination
2011
Structural Insights into Complete Metal Ion Coordination from Ternary Complexes of B Family RB69 DNA Polymerase
Xia S, Wang M, Blaha G, Konigsberg WH, Wang J. Structural Insights into Complete Metal Ion Coordination from Ternary Complexes of B Family RB69 DNA Polymerase. Biochemistry 2011, 50: 9114-9124. PMID: 21923197, PMCID: PMC3760225, DOI: 10.1021/bi201260h.Peer-Reviewed Original ResearchConceptsMetal ionsBond formationHydroxyl groupsCoordination bond lengthsMetal ion coordinationΑ-phosphateB-siteTernary complexMetal ion ACoordination complexesIon coordinationBond lengthsCoordination octahedraIon APhosphorus atomIonic radiusSimultaneous coordinationPhosphodiester bond formationIonsNucleotidyl transferStructural insightsComplexesPyrophosphate productHydrogen-Bonding Capability of a Templating Difluorotoluene Nucleotide Residue in an RB69 DNA Polymerase Ternary Complex
Xia S, Konigsberg WH, Wang J. Hydrogen-Bonding Capability of a Templating Difluorotoluene Nucleotide Residue in an RB69 DNA Polymerase Ternary Complex. Journal Of The American Chemical Society 2011, 133: 10003-10005. PMID: 21667997, PMCID: PMC3139434, DOI: 10.1021/ja2021735.Peer-Reviewed Original ResearchVariation in Mutation Rates Caused by RB69pol Fidelity Mutants Can Be Rationalized on the Basis of Their Kinetic Behavior and Crystal Structures
Xia S, Wang M, Lee HR, Sinha A, Blaha G, Christian T, Wang J, Konigsberg W. Variation in Mutation Rates Caused by RB69pol Fidelity Mutants Can Be Rationalized on the Basis of Their Kinetic Behavior and Crystal Structures. Journal Of Molecular Biology 2011, 406: 558-570. PMID: 21216248, PMCID: PMC3059800, DOI: 10.1016/j.jmb.2010.12.033.Peer-Reviewed Original ResearchConceptsDouble mutantMutation rateAmino acid residuesRB69 DNA polymeraseSingle mutantsMutable sequencesPocket mutantsMutantsAcid residuesState kinetic parametersPrimer extensionT4 phageFidelity mutantsNucleotide residuesIncoming dNTPsDNA polymeraseReversion assayTernary complexComplementary strandCrystal structureResiduesBase selectivityPocketPolymeraseMisincorporation
2010
Insights into Base Selectivity from the 1.8 Å Resolution Structure of an RB69 DNA Polymerase Ternary Complex
Wang M, Xia S, Blaha G, Steitz TA, Konigsberg WH, Wang J. Insights into Base Selectivity from the 1.8 Å Resolution Structure of an RB69 DNA Polymerase Ternary Complex. Biochemistry 2010, 50: 581-590. PMID: 21158418, PMCID: PMC3036992, DOI: 10.1021/bi101192f.Peer-Reviewed Original ResearchSubstitution of Ala for Tyr567 in RB69 DNA Polymerase Allows dAMP and dGMP To Be Inserted opposite Guanidinohydantoin,
Beckman J, Wang M, Blaha G, Wang J, Konigsberg WH. Substitution of Ala for Tyr567 in RB69 DNA Polymerase Allows dAMP and dGMP To Be Inserted opposite Guanidinohydantoin,. Biochemistry 2010, 49: 8554-8563. PMID: 20795733, PMCID: PMC3755731, DOI: 10.1021/bi100913v.Peer-Reviewed Original ResearchSubstitution of Ala for Tyr567 in RB69 DNA Polymerase Allows dAMP To Be Inserted opposite 7,8-Dihydro-8-oxoguanine,
Beckman J, Wang M, Blaha G, Wang J, Konigsberg WH. Substitution of Ala for Tyr567 in RB69 DNA Polymerase Allows dAMP To Be Inserted opposite 7,8-Dihydro-8-oxoguanine,. Biochemistry 2010, 49: 4116-4125. PMID: 20411947, PMCID: PMC2882254, DOI: 10.1021/bi100102s.Peer-Reviewed Original Research
2009
RB69 DNA Polymerase Mutants with Expanded Nascent Base-Pair-Binding Pockets Are Highly Efficient but Have Reduced Base Selectivity
Zhang H, Beckman J, Wang J, Konigsberg W. RB69 DNA Polymerase Mutants with Expanded Nascent Base-Pair-Binding Pockets Are Highly Efficient but Have Reduced Base Selectivity. Biochemistry 2009, 48: 6940-6950. PMID: 19522539, PMCID: PMC2847438, DOI: 10.1021/bi900422b.Peer-Reviewed Original ResearchMeSH KeywordsBacteriophagesBase PairingDNA-Directed DNA PolymeraseKineticsModels, MolecularMutationSpectrometry, FluorescenceConceptsBase pairsCorrect base pairReplicative DNA polymerasesRB69 polRB69 DNA Polymerase MutantsNascent base pairDouble mutantSingle mutantsTriple mutantNumber of substitutionsWild typeMutantsBacteriophage RB69DNA polymerase mutantsPolymerase mutantsDNA polymeraseBinding pocketsNegative selectionDNA polRapid incorporationCatalytic centerLow incorporation efficiencyG mutationSulfolobus solfataricus Dpo4Base discrimination
2006
The ϕ29 DNA polymerase:protein‐primer structure suggests a model for the initiation to elongation transition
Kamtekar S, Berman AJ, Wang J, Lázaro JM, de Vega M, Blanco L, Salas M, Steitz TA. The ϕ29 DNA polymerase:protein‐primer structure suggests a model for the initiation to elongation transition. The EMBO Journal 2006, 25: 1335-1343. PMID: 16511564, PMCID: PMC1422159, DOI: 10.1038/sj.emboj.7601027.Peer-Reviewed Original ResearchConceptsTerminal proteinDNA polymeraseDNA synthesisPrime replicationLinear chromosomesElongation transitionϕ29 DNA polymeraseBacteriophage genomesProtein movesBacteriophage phi29Resolution structureDuplex productsElongation phaseBinding cleftThird domainPolymeraseTemplate DNADuplex DNAPrimer strandSerine hydroxylProteinAbsolute requirementDNAActive siteDomainThe L561A Substitution in the Nascent Base-Pair Binding Pocket of RB69 DNA Polymerase Reduces Base Discrimination †
Zhang H, Rhee C, Bebenek A, Drake JW, Wang J, Konigsberg W. The L561A Substitution in the Nascent Base-Pair Binding Pocket of RB69 DNA Polymerase Reduces Base Discrimination †. Biochemistry 2006, 45: 2211-2220. PMID: 16475809, PMCID: PMC3373012, DOI: 10.1021/bi052099y.Peer-Reviewed Original ResearchAlanineAmino Acid SubstitutionBase Pair MismatchBinding SitesDNA-Directed DNA PolymeraseLeucineModels, MolecularViral Proteins
2005
Hoogsteen base-pairing in DNA replication?
Wang J. Hoogsteen base-pairing in DNA replication? Nature 2005, 437: e6-e7. PMID: 16163299, DOI: 10.1038/nature04199.Peer-Reviewed Original ResearchA specific subdomain in φ29 DNA polymerase confers both processivity and strand-displacement capacity
Rodríguez I, Lázaro JM, Blanco L, Kamtekar S, Berman AJ, Wang J, Steitz TA, Salas M, de Vega M. A specific subdomain in φ29 DNA polymerase confers both processivity and strand-displacement capacity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2005, 102: 6407-6412. PMID: 15845765, PMCID: PMC1088371, DOI: 10.1073/pnas.0500597102.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceBacteriophage T4DNADNA PrimersDNA ReplicationDNA-Directed DNA PolymeraseElectrophoretic Mobility Shift AssayExodeoxyribonucleasesModels, MolecularMolecular Sequence DataMutagenesis, Site-DirectedProtein ConformationProtein Structure, TertiarySequence AlignmentTemplates, GeneticConceptsDNA polymerasePhi29 DNA polymeraseProtein-primed DNA polymerasesStrand-displacement capacityMutant DNA polymerasesΦ29 DNA polymeraseRecent crystallographic studiesDNA binding capacityAsp-398Deletion mutantsStructural insightsSpecific insertionProcessivityPolymeraseStrand displacementFunctional roleAmino acidsPalm subdomainSpecific subdomainsBiochemical analysisDNA synthesisCritical roleRegion 2Crystallographic studiesIntrinsic capacityBase Selectivity Is Impaired by Mutants that Perturb Hydrogen Bonding Networks in the RB69 DNA Polymerase Active Site †
Yang G, Wang J, Konigsberg W. Base Selectivity Is Impaired by Mutants that Perturb Hydrogen Bonding Networks in the RB69 DNA Polymerase Active Site †. Biochemistry 2005, 44: 3338-3346. PMID: 15736944, DOI: 10.1021/bi047921x.Peer-Reviewed Original ResearchMeSH KeywordsAlanineAmino Acid SubstitutionBase Pair MismatchBinding SitesDeoxyadenine NucleotidesDeoxycytosine NucleotidesDeoxyguanine NucleotidesDNA-Directed DNA PolymeraseEnterobacterHydrogen BondingKineticsNucleotidesPhenylalanineSubstrate SpecificityThymine NucleotidesTolueneTyrosineViral ProteinsConceptsRB69 polRapid chemical quenchHydrogen bonding networkSet of mutantsStopped-flow fluorescencePutative conformational changesPhosphoryl transfer reactionsPolymerase active siteRB69 DNA polymeraseDNA polymerase active siteChemical quenchMolecular basisBonding networkNoncomplementary dNTPsMutantsTransfer reactionsExo enzymesState kinetic parametersConformational changesMismatched basesActive siteExo formCrystal structureDNA polymeraseNucleoside triphosphates