ArticleNature structural & molecular biology2010
Structural basis of HIV-1 resistance to AZT by excision.
Article in Nature structural & molecular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
What it found
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The trial behind it
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Who cites it
68 citing papers in PubMed, 119 citations in OpenAlex.
- Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase.PloS one · 2012Trial
- Unraveling the Mechanism of HIV-1 Hypersusceptibility to Tenofovir Imparted by Islatravir Resistance Mutations.bioRxiv : the preprint server for biology · 2026Article
- Kinetic coevolutionary models predict the temporal emergence of HIV-1 resistance mutations under drug selection pressure.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Evolution of drug resistance drives destabilization of flap region dynamics in HIV-1 protease.Biophysical reports · 2023Article
- 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
- Insights into HIV-1 Reverse Transcriptase (RT) Inhibition and Drug Resistance from Thirty Years of Structural Studies.Viruses · 2022Review
- A Combination of Amino Acid Mutations Leads to Resistance to Multiple Nucleoside Analogs in Reverse Transcriptases from HIV-1 Subtypes B and C.Antimicrobial agents and chemotherapy · 2022Article
- Sampling of Protein Conformational Space Using Hybrid Simulations: A Critical Assessment of Recent Methods.Frontiers in molecular biosciences · 2022Article
- Sliding of HIV-1 reverse transcriptase over DNA creates a transient P pocket - targeting P-pocket by fragment screening.Nature communications · 2021Article
- Avoiding Drug Resistance in HIV Reverse Transcriptase.Chemical reviews · 2021Review
- Large Multidomain Protein NMR: HIV-1 Reverse Transcriptase Precursor in Solution.International journal of molecular sciences · 2020Review
- Post-Catalytic Complexes with Emtricitabine or Stavudine and HIV-1 Reverse Transcriptase Reveal New Mechanistic Insights for Nucleotide Incorporation and Drug Resistance.Molecules (Basel, Switzerland) · 2020Article
- Mechanistic cross-talk between DNA/RNA polymerase enzyme kinetics and nucleotide substrate availability in cells: Implications for polymerase inhibitor discovery.The Journal of biological chemistry · 2020Review
- Nucleocapsid Protein Precursors NCp9 and NCp15 Suppress ATP-Mediated Rescue of AZT-Terminated Primers by HIV-1 Reverse Transcriptase.Antimicrobial agents and chemotherapy · 2020Article
- Resistance to excision determines efficiency of hepatitis C virus RNA-dependent RNA polymerase inhibition by nucleotide analogs.The Journal of biological chemistry · 2020Article
- Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine.Scientific reports · 2020Article
- Structural Basis of HIV-1 Inhibition by Nucleotide-Competing Reverse Transcriptase Inhibitor INDOPY-1.Journal of medicinal chemistry · 2019Article
- Determinants of Active-Site Inhibitor Interaction with HIV-1 RNase H.ACS infectious diseases · 2019Article
- Review
- Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs.Journal of virology · 2019Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
Abstract
Human immunodeficiency virus (HIV-1) develops resistance to 3'-azido-2',3'-deoxythymidine (AZT, zidovudine) by acquiring mutations in reverse transcriptase that enhance the ATP-mediated excision of AZT monophosphate from the 3' end of the primer. The excision reaction occurs at the dNTP-binding site, uses ATP as a pyrophosphate donor, unblocks the primer terminus and allows reverse transcriptase to continue viral DNA synthesis. The excision product is AZT adenosine dinucleoside tetraphosphate (AZTppppA). We determined five crystal structures: wild-type reverse transcriptase-double-stranded DNA (RT-dsDNA)-AZTppppA; AZT-resistant (AZTr; M41L D67N K70R T215Y K219Q) RT-dsDNA-AZTppppA; AZTr RT-dsDNA terminated with AZT at dNTP- and primer-binding sites; and AZTr apo reverse transcriptase. The AMP part of AZTppppA bound differently to wild-type and AZTr reverse transcriptases, whereas the AZT triphosphate part bound the two enzymes similarly. Thus, the resistance mutations create a high-affinity ATP-binding site. The structure of the site provides an opportunity to design inhibitors of AZT-monophosphate excision.
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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.