ArticleNucleic acids research2014
Structural and kinetic insights into binding and incorporation of L-nucleotide analogs by a Y-family DNA polymerase.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 24 citations in OpenAlex.
- Residues in the little finger domain of the Y-family Dpo4 DNA polymerase communicate to restrict synthesis past 8-oxoguanine lesions.Nucleic acids research · 2025Article
- Structural basis for processive daughter-strand synthesis and proofreading by the human leading-strand DNA polymerase Pol ε.Nature structural & molecular biology · 2024Article
- Replicative bypass studies of l-deoxyribonucleosides in Vitro and in E. coli cell.Scientific reports · 2022Article
- Structural basis of HIV inhibition by L-nucleosides: Opportunities for drug development and repurposing.Drug discovery today · 2022Review
- Compatibility and Fidelity of Mirror-Image Thymidine in Transcription Events by T7 RNA Polymerase.Molecular therapy. Nucleic acids · 2020Article
- A polar filter in DNA polymerases prevents ribonucleotide incorporation.Nucleic acids research · 2019Article
- Elucidating molecular interactions ofCommunications biology · 2019Article
- Structural basis for the D-stereoselectivity of human DNA polymerase β.Nucleic acids research · 2017Article
- Advances in Structural and Single-Molecule Methods for Investigating DNA Lesion Bypass and Repair Polymerases.Chemical research in toxicology · 2017Article
- Significant impact of divalent metal ions on the fidelity, sugar selectivity, and drug incorporation efficiency of human PrimPol.DNA repair · 2017Article
- Computational Evaluation of Nucleotide Insertion Opposite Expanded and Widened DNA by the Translesion Synthesis Polymerase Dpo4.Molecules (Basel, Switzerland) · 2016Article
- Mechanistic Basis for the Bypass of a Bulky DNA Adduct Catalyzed by a Y-Family DNA Polymerase.Journal of the American Chemical Society · 2015Article
- Ribonucleotides in bacterial DNA.Critical reviews in biochemistry and molecular biology · 2015Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Considering that all natural nucleotides (D-dNTPs) and the building blocks (D-dNMPs) of DNA chains possess D-stereochemistry, DNA polymerases and reverse transcriptases (RTs) likely possess strongD-stereoselectivity by preferably binding and incorporating D-dNTPs over unnatural L-dNTPs during DNA synthesis. Surprisingly, a structural basis for the discrimination against L-dNTPs by DNA polymerases or RTs has not been established although L-deoxycytidine analogs (lamivudine and emtricitabine) and L-thymidine (telbivudine) have been widely used as antiviral drugs for years. Here we report seven high-resolution ternary crystal structures of a prototype Y-family DNA polymerase, DNA, and D-dCTP, D-dCDP, L-dCDP, or the diphosphates and triphosphates of lamivudine and emtricitabine. These structures reveal that relative to D-dCTP, each of these L-nucleotides has its sugar ring rotated by 180° with an unusual O4'-endo sugar puckering and exhibits multiple triphosphate-binding conformations within the active site of the polymerase. Such rare binding modes significantly decrease the incorporation rates and efficiencies of these L-nucleotides catalyzed by the polymerase.
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Registered trials
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.