2024
Modifying the Basicity of the dNTP Leaving Group Modulates Precatalytic Conformational Changes of DNA Polymerase β
Alnajjar K, Wang K, Alvarado-Cruz I, Chavira C, Negahbani A, Nakhjiri M, Minard C, Garcia-Barboza B, Kashemirov B, McKenna C, Goodman M, Sweasy J. Modifying the Basicity of the dNTP Leaving Group Modulates Precatalytic Conformational Changes of DNA Polymerase β. Biochemistry 2024, 63: 1412-1422. PMID: 38780930, PMCID: PMC11155676, DOI: 10.1021/acs.biochem.4c00065.Peer-Reviewed Original ResearchDNA polymerase BPolymerase BPol-BBase excision DNA repair pathwayLinear free energy relationshipGapped DNA substratesRemoval of damaged DNA basesFree energy relationshipConformational changesChemical transition stateAccumulation of mutationsDNA repair pathwaysDamaged DNA basesGroup basicityCorrect nucleotideDNA substratesIncoming nucleotideTransition stateEnergy relationshipFingers subdomainRepair pathwaysSubstrate selectivityNucleotideTriphosphate moietyCatalytic function
2017
Defective Nucleotide Release by DNA Polymerase β Mutator Variant E288K Is the Basis of Its Low Fidelity
Mahmoud MM, Schechter A, Alnajjar KS, Huang J, Towle-Weicksel J, Eckenroth BE, Doublié S, Sweasy JB. Defective Nucleotide Release by DNA Polymerase β Mutator Variant E288K Is the Basis of Its Low Fidelity. Biochemistry 2017, 56: 5550-5559. PMID: 28945359, PMCID: PMC5654646, DOI: 10.1021/acs.biochem.7b00869.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SubstitutionBiocatalysisColonic NeoplasmsDNADNA Polymerase betaDNA RepairDNA ReplicationEnzyme StabilityFluorescent DyesHumansKineticsModels, MolecularMutagenesis, Site-DirectedMutationNaphthalenesulfonatesNeoplasm ProteinsP-DimethylaminoazobenzeneProtein ConformationProtein Interaction Domains and MotifsProtein RefoldingRecombinant ProteinsSubstrate Specificity