ArticleACS chemical biology2016
Conformational States of HIV-1 Reverse Transcriptase for Nucleotide Incorporation vs Pyrophosphorolysis-Binding of Foscarnet.
Article in ACS chemical biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 41 citations in OpenAlex.
- A novel aptamer-based dNTP assay reveals that intact HIV virions are highly stable and do not contain enough dNTPs to support DNA synthesis.Journal of virology · 2025Article
- Structural basis of deoxynucleotide addition by HIV-1 RT during reverse transcription.Nature communications · 2024Article
- Small Molecule Drugs Targeting Viral Polymerases.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Structural Insights into Protein-Aptamer Recognitions Emerged from Experimental and Computational Studies.International journal of molecular sciences · 2023Review
- Transposon control as a checkpoint for tissue regeneration.Development (Cambridge, England) · 2022Article
- Article
- Cryo-EM structures of wild-type and E138K/M184I mutant HIV-1 RT/DNA complexed with inhibitors doravirine and rilpivirine.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Human endogenous retrovirus-K (HERV-K) reverse transcriptase (RT) structure and biochemistry reveals remarkable similarities to HIV-1 RT and opportunities for HERV-K-specific inhibition.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Structural basis of HIV inhibition by L-nucleosides: Opportunities for drug development and repurposing.Drug discovery today · 2022Review
- Selection of Primer-Template Sequences That Bind with Enhanced Affinity to Vaccinia Virus E9 DNA Polymerase.Viruses · 2022Article
- Sliding of HIV-1 reverse transcriptase over DNA creates a transient P pocket - targeting P-pocket by fragment screening.Nature communications · 2021Article
- HIV-1 gp120 Antagonists Also Inhibit HIV-1 Reverse Transcriptase by Bridging the NNRTI and NRTI Sites.Journal of medicinal chemistry · 2021Article
- NMPylation and de-NMPylation of SARS-CoV-2 nsp9 by the NiRAN domain.Nucleic acids research · 2021Article
- Structural understanding of non-nucleoside inhibition in an elongating herpesvirus polymerase.Nature communications · 2021Article
- Evolving understanding of HIV-1 reverse transcriptase structure, function, inhibition, and resistance.Current opinion in structural biology · 2020Review
- Integrative structural biology studies of HIV-1 reverse transcriptase binding to a high-affinity DNA aptamer.Current research in structural biology · 2020Article
- Structural Basis of HIV-1 Inhibition by Nucleotide-Competing Reverse Transcriptase Inhibitor INDOPY-1.Journal of medicinal chemistry · 2019Article
- Selection of 2'-Deoxy-2'-Fluoroarabino Nucleic Acid (FANA) Aptamers That Bind HIV-1 Integrase with Picomolar Affinity.ACS chemical biology · 2019Article
- Non-nucleoside Reverse Transcriptase Inhibitors Inhibit Reverse Transcriptase through a Mutually Exclusive Interaction with Divalent Cation-dNTP Complexes.Biochemistry · 2019Article
- Structure of HIV-1 reverse transcriptase/d4TTP complex: Novel DNA cross-linking site and pH-dependent conformational changes.Protein science : a publication of the Protein Society · 2019Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
Abstract
HIV-1 reverse transcriptase (RT) catalytically incorporates individual nucleotides into a viral DNA strand complementing an RNA or DNA template strand; the polymerase active site of RT adopts multiple conformational and structural states while performing this task. The states associated are dNTP binding at the N site, catalytic incorporation of a nucleotide, release of a pyrophosphate, and translocation of the primer 3'-end to the P site. Structural characterization of each of these states may help in understanding the molecular mechanisms of drug activity and resistance and in developing new RT inhibitors. Using a 38-mer DNA template-primer aptamer as the substrate mimic, we crystallized an RT/dsDNA complex that is catalytically active, yet translocation-incompetent in crystals. The ability of RT to perform dNTP binding and incorporation in crystals permitted obtaining a series of structures: (I) RT/DNA (P-site), (II) RT/DNA/AZTTP ternary, (III) RT/AZT-terminated DNA (N-site), and (IV) RT/AZT-terminated DNA (N-site)/foscarnet complexes. The stable N-site complex permitted the binding of foscarnet as a pyrophosphate mimic. The Mg(2+) ions dissociated after catalytic addition of AZTMP in the pretranslocated structure III, whereas ions A and B had re-entered the active site to bind foscarnet in structure IV. The binding of foscarnet involves chelation with the Mg(2+) (B) ion and interactions with K65 and R72. The analysis of interactions of foscarnet and the recently discovered nucleotide-competing RT inhibitor (NcRTI) α-T-CNP in two different conformational states of the enzyme provides insights for developing new classes of polymerase active site RT inhibitors.
Indexed as
Identifiers
What OpenQuestion holds
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.