ArticleStructure (London, England : 1993)2012
Structures of dNTP intermediate states during DNA polymerase active site assembly.
Article in Structure (London, England : 1993), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed.
- The S180R Human Germline Variant of DNA Polymerase β Is a Low Fidelity Enzyme with Reduced Flexibility of the Fingers Domain.Biochemistry · 2026Article
- Structural basis of multitasking by the apicoplast DNA polymerase from Plasmodium falciparum.Nucleic acids research · 2025Article
- Structural Insights into the Nonmutagenicity of 2-Haloacetophenone.Molecules (Basel, Switzerland) · 2025Article
- Modifying the Basicity of the dNTP Leaving Group Modulates Precatalytic Conformational Changes of DNA Polymerase β.Biochemistry · 2024Article
- 3'dNTP Binding Is Modulated during Primer Synthesis and Translesion by Human PrimPol.International journal of molecular sciences · 2023Article
- Structural Insights into Phosphorylation-Mediated Polymerase Function Loss for DNA PolymeraseInternational journal of molecular sciences · 2023Article
- Review
- History of DNA polymerase β X-ray crystallography.DNA repair · 2020Review
- DNA polymerase β: Closing the gap between structure and function.DNA repair · 2020Review
- Using single-molecule FRET to probe the nucleotide-dependent conformational landscape of polymerase β-DNA complexes.The Journal of biological chemistry · 2020Article
- Structural insights into the promutagenic bypass of the major cisplatin-induced DNA lesion.The Biochemical journal · 2020Article
- Molecular and structural characterization of oxidized ribonucleotide insertion into DNA by human DNA polymerase β.The Journal of biological chemistry · 2020Article
- NMR and computational methods for molecular resolution of allosteric pathways in enzyme complexes.Biophysical reviews · 2020Review
- Structure and function relationships in mammalian DNA polymerases.Cellular and molecular life sciences : CMLS · 2020Review
- Structural evidence for an inThe Journal of biological chemistry · 2019Article
- A guardian residue hinders insertion of a Fapy•dGTP analog by modulating the open-closed DNA polymerase transition.Nucleic acids research · 2019Article
- Structural and Kinetic Studies of the Effect of Guanine N7 Alkylation and Metal Cofactors on DNA Replication.Biochemistry · 2018Article
- Mapping Functional Substrate-Enzyme Interactions in the pol β Active Site through Chemical Biology: Structural Responses to Acidity Modification of Incoming dNTPs.Biochemistry · 2018Article
- Activity and fidelity of human DNA polymerase α depend on primer structure.The Journal of biological chemistry · 2018Article
- Template-Independent Enzymatic Oligonucleotide Synthesis (TiEOS): Its History, Prospects, and Challenges.Biochemistry · 2018Review
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3 authors.
Funding
Abstract
DNA polymerase and substrate conformational changes are essential for high-fidelity DNA synthesis. Structures of DNA polymerase (pol) β in complex with DNA show the enzyme in an "open" conformation. Subsequent to binding the nucleotide, the polymerase "closes" around the nascent base pair with two metals positioned for chemistry. However, structures of substrate/active site intermediates prior to closure are lacking. By destabilizing the closed complex, we determined unique ternary complex structures of pol β with correct and incorrect incoming nucleotides bound to the open conformation. These structures reveal that Watson-Crick hydrogen bonding is assessed upon initial complex formation. Importantly, nucleotide-bound states representing intermediate metal coordination states occur with active site assembly. The correct, but not incorrect, nucleotide maintains Watson-Crick hydrogen bonds during interconversion of these states. These structures indicate that the triphosphate of the incoming nucleotide undergoes rearrangement prior to closure, providing an opportunity to deter misinsertion and increase fidelity.
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