Evidence map›Paper›PMID 31943114›Full record

ArticleNucleic acids research2020

Binding interface and impact on protease cleavage for an RNA aptamer to HIV-1 reverse transcriptase.

Phuong D M Nguyen, Jie Zheng, Thomas J Gremminger, Liming Qiu, Dong Zhang, Steve Tuske, Margaret J Lange, Patrick R Griffin, Eddy Arnold, Shi-Jie Chen and 3 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.9field-weighted citation impact, top 14% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 32 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Article
  6. Aptamers-Diagnostic and Therapeutic Solution in SARS-CoV-2.International journal of molecular sciences · 2022
    Review
  7. Review
  8. Article
  9. Article
  10. Aptamers for Anti-Viral Therapeutics and Diagnostics.International journal of molecular sciences · 2021
    Review
  11. Artificial Intelligence in Aptamer-Target Binding Prediction.International journal of molecular sciences · 2021
    Review
  12. Review
  13. Review
  14. Review
  15. Extended Interactions between HIV-1 Viral RNA and tRNAInternational journal of molecular sciences · 2020
    Article
  16. Methods and Applications of In Silico Aptamer Design and Modeling.International journal of molecular sciences · 2020
    Review
  17. Article
  18. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 4 institutions in 1 country.

Phuong D M NguyenDepartment of Biochemistry, University of Missouri, Columbia, MO 65211, USA.
Jie ZhengDepartment of Molecular Medicine, The Scripps Research Institute, Jupiter, FL 33458, USA.
Thomas J GremmingerDepartment of Biochemistry, University of Missouri, Columbia, MO 65211, USA.
Liming QiuDalton Cardiovascular Research Center, University Missouri, Columbia, MO 65211, USA.
Dong ZhangDepartment of Physics and Astronomy, University Missouri, Columbia, MO 65211, USA.
Steve TuskeCenter for Advanced Biotechnology & Medicine, and Department of Chemistry & Chemical Biology, Rutgers University, Piscataway, NJ 08854, USA.
Margaret J LangeDepartment of Molecular Microbiology & Immunology, University Missouri, Columbia, MO 65211, USA.
Patrick R GriffinDepartment of Molecular Medicine, The Scripps Research Institute, Jupiter, FL 33458, USA.
Eddy ArnoldCenter for Advanced Biotechnology & Medicine, and Department of Chemistry & Chemical Biology, Rutgers University, Piscataway, NJ 08854, USA.
Shi-Jie ChenDepartment of Biochemistry, University of Missouri, Columbia, MO 65211, USA.
Xiaoqin ZouDepartment of Biochemistry, University of Missouri, Columbia, MO 65211, USA.
Xiao HengDepartment of Biochemistry, University of Missouri, Columbia, MO 65211, USA.
Donald H BurkeDepartment of Biochemistry, University of Missouri, Columbia, MO 65211, USA.
University of Missouri · USRutgers, The State University of New Jersey · USScripps Research Institute · USUniversity of Missouri Health System · US

Funding

X-ray Crystallographic Fragment Screening CoreU54AI150472 · NIAID · SEATTLE CHILDREN'S HOSPITAL · PI SARAFIANOS, STEFAN G, TORBETT, BRUCE EDWARD · 2019 to 2021
$15.7M
X-ray Crystallographic Fragment Screening CoreU54GM103368 · NIGMS · SCRIPPS RESEARCH INSTITUTE, THE · PI SARAFIANOS, STEFAN G, TORBETT, BRUCE EDWARD · 2017 to 2018
$11.1M
Molecular Genetic Analysis of Mycobacterium TuberculosisR37AI026170 · NIAID · ALBERT EINSTEIN COL OF MED YESHIVA UNIV · PI WILLIAM Robert JACOBS · 2004 to 2026
$7.7M
Gene Therapy for HIV Using Aptamers that Target Reverse TranscriptaseR01AI074389 · NIAID · UNIVERSITY OF MISSOURI-COLUMBIA · PI BURKE, DONALD H · 2008 to 2017
$4.5M
STRUCTURES OF HIV REVERSE TRANSCRIPTASE WITH SUBSTRATESR01AI027690 · NIAID · UNIV OF MED/DENT NJ-R W JOHNSON MED SCH · PI EDWARD ARNOLD · 1989 to 2026
$4.3M
Statistical Mechanics of RNA FoldingR01GM063732 · NIGMS · UNIVERSITY OF MISSOURI-COLUMBIA · PI CHEN, SHI-JIE · 2003 to 2018
$3.2M
Database and software development for protein-nucleic acid structure predicationR01GM109980 · NIGMS · UNIVERSITY OF MISSOURI-COLUMBIA · PI ZOU, XIAOQIN · 2015 to 2019
$1.5M
New computational tools for predicting ion effects in RNA structuresR01GM117059 · NIGMS · UNIVERSITY OF MISSOURI-COLUMBIA · PI CHEN, SHI-JIE · 2017 to 2020
$1.2M
Structural basis of the HIV-1 PBS-segment mediated RHA recruitment during assembly to bolster virus infectivityR01AI150460 · NIAID · UNIVERSITY OF MISSOURI-COLUMBIA · PI HENG, XIAO · 2019 to 2021
$916k
NIAID NIH HHS R01 AI027690NIAID NIH HHS R01 AI074389NIAID NIH HHS R01 AI150460NIAID NIH HHS R37 AI026170NIAID NIH HHS U54 AI150472NIGMS NIH HHS R01 GM063732NIGMS NIH HHS R01 GM109980NIGMS NIH HHS R01 GM117059NIGMS NIH HHS U54 GM103368
6 · The paper itself

Abstract

RNA aptamers that bind HIV-1 reverse transcriptase (RT) inhibit RT in enzymatic and viral replication assays. Some aptamers inhibit RT from only a few viral clades, while others show broad-spectrum inhibition. Biophysical determinants of recognition specificity are poorly understood. We investigated the interface between HIV-1 RT and a broad-spectrum UCAA-family aptamer. SAR and hydroxyl radical probing identified aptamer structural elements critical for inhibition and established the role of signature UCAA bulge motif in RT-aptamer interaction. HDX footprinting on RT ± aptamer shows strong contacts with both subunits, especially near the C-terminus of p51. Alanine scanning revealed decreased inhibition by the aptamer for mutants P420A, L422A and K424A. 2D proton nuclear magnetic resonance and SAXS data provided constraints on the solution structure of the aptamer and enable computational modeling of the docked complex with RT. Surprisingly, the aptamer enhanced proteolytic cleavage of precursor p66/p66 by HIV-1 protease, suggesting that it stabilizes the productive conformation to allow maturation. These results illuminate features at the RT-aptamer interface that govern recognition specificity by a broad-spectrum antiviral aptamer, and they open new possibilities for accelerating RT maturation and interfering with viral replication.

Indexed as

Aptamers, NucleotideHIV ProteaseHIV Reverse TranscriptaseMolecular Docking SimulationMutagenesisMutant ProteinsProtein BindingProtein MultimerizationReverse Transcriptase InhibitorsAptamers, NucleotideHIV ProteaseHIV Reverse TranscriptaseMutant Proteinsreverse transcriptase, Human immunodeficiency virus 1Reverse Transcriptase Inhibitors

Identifiers

PMID31943114
PMCPMC7049723
OpenAlexW3000543841

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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.