ArticleBiochemistry2014
Transition state in DNA polymerase β catalysis: rate-limiting chemistry altered by base-pair configuration.
Article in Biochemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- Biochemical, structural and mutational landscapes of base excision repair enzymes and cancer: from atomic resolution to tumor signatures.International journal of radiation biology · 2026Review
- Conformational gating governs nucleotide incorporation by a DNA-crosslinked polymerase.Nucleic acids research · 2026Article
- Modifying the Basicity of the dNTP Leaving Group Modulates Precatalytic Conformational Changes of DNA Polymerase β.Biochemistry · 2024Article
- Trivalent rare earth metal cofactors confer rapid NP-DNA polymerase activity.Science (New York, N.Y.) · 2023Article
- Kinetic Effects of β,γ-Modified Deoxynucleoside 5'-Triphosphate Analogues on RNA-Catalyzed Polymerization of DNA.Biochemistry · 2021Article
- Completing the β,γ-CXY-dNTP Stereochemical Probe Toolkit: Synthetic Access to the dCTP Diastereomers andThe Journal of organic chemistry · 2020Article
- Nucleotide Analog ARL67156 as a Lead Structure for the Development of CD39 and Dual CD39/CD73 Ectonucleotidase Inhibitors.Frontiers in pharmacology · 2020Article
- A pre-catalytic non-covalent step governs DNA polymerase β fidelity.Nucleic acids research · 2019Article
- A Transition-State Perspective on Y-Family DNA Polymerase η Fidelity in Comparison with X-Family DNA Polymerases λ and β.Biochemistry · 2019Article
- Mapping Functional Substrate-Enzyme Interactions in the pol β Active Site through Chemical Biology: Structural Responses to Acidity Modification of Incoming dNTPs.Biochemistry · 2018Article
- Probing DNA Base-Dependent Leaving Group Kinetic Effects on the DNA Polymerase Transition State.Biochemistry · 2018Article
- A Tool for the Import of Natural and Unnatural Nucleoside Triphosphates into Bacteria.Journal of the American Chemical Society · 2018Article
- Theoretical Studies on Mechanism of Inactivation of Kanamycin A by 4'-O-Nucleotidyltransferase.Frontiers in chemistry · 2018Article
- DNA Polymerase β Cancer-Associated Variant I260M Exhibits Nonspecific Selectivity toward the β-γ Bridging Group of the Incoming dNTP.Biochemistry · 2017Article
- Modulating the DNA polymerase β reaction equilibrium to dissect the reverse reaction.Nature chemical biology · 2017Article
- A Change in the Rate-Determining Step of Polymerization by the K289M DNA Polymerase β Cancer-Associated Variant.Biochemistry · 2017Article
- Chemical Stabilization of Unnatural Nucleotide Triphosphates for the in Vivo Expansion of the Genetic Alphabet.Journal of the American Chemical Society · 2017Article
- Uniform Free-Energy Profiles of the P-O Bond Formation and Cleavage Reactions Catalyzed by DNA Polymerases β and λ.The journal of physical chemistry. B · 2016Article
- Functional interplay between NTP leaving group and base pair recognition during RNA polymerase II nucleotide incorporation revealed by methylene substitution.Nucleic acids research · 2016Article
- New structural snapshots provide molecular insights into the mechanism of high fidelity DNA synthesis.DNA repair · 2015Review
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Kinetics studies of dNTP analogues having pyrophosphate-mimicking β,γ-pCXYp leaving groups with variable X and Y substitution reveal striking differences in the chemical transition-state energy for DNA polymerase β that depend on all aspects of base-pairing configurations, including whether the incoming dNTP is a purine or pyrimidine and if base-pairings are right (T•A and G•C) or wrong (T•G and G•T). Brønsted plots of the catalytic rate constant (log(kpol)) versus pKa4 for the leaving group exhibit linear free energy relationships (LFERs) with negative slopes ranging from -0.6 to -2.0, consistent with chemical rate-determining transition-states in which the active-site adjusts to charge-stabilization demand during chemistry depending on base-pair configuration. The Brønsted slopes as well as the intercepts differ dramatically and provide the first direct evidence that dNTP base recognition by the enzyme-primer-template complex triggers a conformational change in the catalytic region of the active-site that significantly modifies the rate-determining chemical step.
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Registered trials
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