ArticleProceedings of the National Academy of Sciences of the United States of America2010
Structural basis for the synthesis of nucleobase modified DNA by Thermus aquaticus DNA polymerase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. 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, 82 citations in OpenAlex.
- Error-Prone DNA Synthesis on Click-Ligated Templates.Doklady. Biochemistry and biophysics · 2024Article
- Non-Covalent Interactions between dUTP C5-Substituents and DNA Polymerase Decrease PCR Efficiency.International journal of molecular sciences · 2023Article
- Synthesis of Polyanionic C5-Modified 2'-Deoxyuridine and 2'-Deoxycytidine-5'-Triphosphates and Their Properties as Substrates for DNA Polymerases.Molecules (Basel, Switzerland) · 2021Article
- Modified nucleoside triphosphates in bacterial research forRSC chemical biology · 2020Article
- Key aurophilic motif for robust quantum-tunneling-based characterization of a nucleoside analogue marker.Chemical science · 2020Article
- Review
- The Structural Basis for Processing of Unnatural Base Pairs by DNA Polymerases.Chemistry (Weinheim an der Bergstrasse, Germany) · 2020Review
- Enzymatic synthesis and modification of high molecular weight DNA using terminal deoxynucleotidyl transferase.Methods in enzymology · 2019Article
- 2-Allyl- and Propargylamino-dATPs for Site-Specific Enzymatic Introduction of a Single Modification in the Minor Groove of DNA.Chemistry (Weinheim an der Bergstrasse, Germany) · 2018Article
- Snapshots of a modified nucleotide moving through the confines of a DNA polymerase.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Recent progress in dissecting molecular recognition by DNA polymerases with non-native substrates.Current opinion in chemical biology · 2017Review
- Exploring the Chemistry of Genetic Information Storage and Propagation through Polymerase Engineering.Accounts of chemical research · 2017Review
- Article
- 2-Substituted dATP Derivatives as Building Blocks for Polymerase-Catalyzed Synthesis of DNA Modified in the Minor Groove.Angewandte Chemie (International ed. in English) · 2016Article
- The Toolbox for Modified Aptamers.Molecular biotechnology · 2016Review
- The expanded genetic alphabet.Angewandte Chemie (International ed. in English) · 2015Review
- C(α) torsion angles as a flexible criterion to extract secrets from a molecular dynamics simulation.Journal of molecular modeling · 2014Article
- A new building block for DNA network formation by self-assembly and polymerase chain reaction.Beilstein journal of organic chemistry · 2014Article
- DNA ligase-mediated translation of DNA into densely functionalized nucleic acid polymers.Journal of the American Chemical Society · 2013Article
- Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Numerous 2'-deoxynucleoside triphosphates (dNTPs) that are functionalized with spacious modifications such as dyes and affinity tags like biotin are substrates for DNA polymerases. They are widely employed in many cutting-edge technologies like advanced DNA sequencing approaches, microarrays, and single molecule techniques. Modifications attached to the nucleobase are accepted by many DNA polymerases, and thus, dNTPs bearing nucleobase modifications are predominantly employed. When pyrimidines are used the modifications are almost exclusively at the C5 position to avoid disturbing of Watson-Crick base pairing ability. However, the detailed molecular mechanism by which C5 modifications are processed by a DNA polymerase is poorly understood. Here, we present the first crystal structures of a DNA polymerase from Thermus aquaticus processing two C5 modified substrates that are accepted by the enzyme with different efficiencies. The structures were obtained as ternary complex of the enzyme bound to primer/template duplex with the respective modified dNTP in position poised for catalysis leading to incorporation. Thus, the study provides insights into the incorporation mechanism of the modified nucleotides elucidating how bulky modifications are accepted by the enzyme. The structures show a varied degree of perturbation of the enzyme substrate complexes depending on the nature of the modifications suggesting design principles for future developments of modified substrates for DNA polymerases.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.