ArticleNucleic acids research2008
Crystal engineering of HIV-1 reverse transcriptase for structure-based drug design.
Article in Nucleic acids research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 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
62 citing papers in PubMed, 89 citations in OpenAlex.
- Development of Human Immunodeficiency Virus Type 1 Resistance to 4'-Ethynyl-2-Fluoro-2'-Deoxyadenosine Starting with Wild-Type or Nucleoside Reverse Transcriptase Inhibitor-Resistant Strains.Antimicrobial agents and chemotherapy · 2021Trial
- Development of enhanced HIV-1 non-nucleoside reverse transcriptase inhibitors with improved resistance and pharmacokinetic profiles.Science advances · 2025Article
- Halo Library, a Tool for Rapid Identification of Ligand Binding Sites on Proteins Using Crystallographic Fragment Screening.Journal of medicinal chemistry · 2023Article
- Targeting HIV-1 Reverse Transcriptase Using a Fragment-Based Approach.Molecules (Basel, Switzerland) · 2023Article
- Finding a chink in the armor: Update, limitations, and challenges toward successful antivirals against flaviviruses.PLoS neglected tropical diseases · 2022Review
- 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
- Co-crystallization with diabodies: A case study for the introduction of synthetic symmetry.Structure (London, England : 1993) · 2021Article
- 2,4,5-Trisubstituted Pyrimidines as Potent HIV-1 NNRTIs: Rational Design, Synthesis, Activity Evaluation, and Crystallographic Studies.Journal of medicinal chemistry · 2021Article
- Discovery and Characterization of Fluorine-Substituted Diarylpyrimidine Derivatives as Novel HIV-1 NNRTIs with Highly Improved Resistance Profiles and Low Activity for the hERG Ion Channel.Journal of medicinal chemistry · 2020Article
- Integrative structural biology studies of HIV-1 reverse transcriptase binding to a high-affinity DNA aptamer.Current research in structural biology · 2020Article
- Spatial domain organization in the HIV-1 reverse transcriptase p66 homodimer precursor probed by double electron-electron resonance EPR.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Structural insights into the recognition of nucleoside reverse transcriptase inhibitors by HIV-1 reverse transcriptase: First crystal structures with reverse transcriptase and the active triphosphate forms of lamivudine and emtricitabine.Protein science : a publication of the Protein Society · 2019Article
- The Journey of HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) from Lab to Clinic.Journal of medicinal chemistry · 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
- Lattice engineering enables definition of molecular features allowing for potent small-molecule inhibition of HIV-1 entry.Nature communications · 2019Article
- Article
- Developing and Evaluating Inhibitors against the RNase H Active Site of HIV-1 Reverse Transcriptase.Journal of virology · 2018Article
- HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir.Scientific reports · 2018Article
- Design, synthesis and biological evaluations of N-Hydroxy thienopyrimidine-2,4-diones as inhibitors of HIV reverse transcriptase-associated RNase H.European journal of medicinal chemistry · 2017Article
2 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
11 authors at 1 institution in 1 country.
Funding
Abstract
HIV-1 reverse transcriptase (RT) is a primary target for anti-AIDS drugs. Structures of HIV-1 RT, usually determined at approximately 2.5-3.0 A resolution, are important for understanding enzyme function and mechanisms of drug resistance in addition to being helpful in the design of RT inhibitors. Despite hundreds of attempts, it was not possible to obtain the structure of a complex of HIV-1 RT with TMC278, a nonnucleoside RT inhibitor (NNRTI) in advanced clinical trials. A systematic and iterative protein crystal engineering approach was developed to optimize RT for obtaining crystals in complexes with TMC278 and other NNRTIs that diffract X-rays to 1.8 A resolution. Another form of engineered RT was optimized to produce a high-resolution apo-RT crystal form, reported here at 1.85 A resolution, with a distinct RT conformation. Engineered RTs were mutagenized using a new, flexible and cost effective method called methylated overlap-extension ligation independent cloning. Our analysis suggests that reducing the solvent content, increasing lattice contacts, and stabilizing the internal low-energy conformations of RT are critical for the growth of crystals that diffract to high resolution. The new RTs enable rapid crystallization and yield high-resolution structures that are useful in designing/developing new anti-AIDS drugs.
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.