ArticleNucleic acids research2017
Coordination between the polymerase and RNase H activity of HIV-1 reverse transcriptase.
Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 35 citations in OpenAlex.
- Comprehensive Assessment of Force-Field Performance in Molecular Dynamics Simulations of DNA/RNA Hybrid Duplexes.Journal of chemical theory and computation · 2024Article
- Structural and computational studies of HIV-1 RNA.RNA biology · 2024Review
- Review
- Interlocking activities of DNA polymerase β in the base excision repair pathway.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Role of salt-bridging interactions in recognition of viral RNA by arginine-rich peptides.Biophysical journal · 2021Article
- Structures of Substrate Complexes of Foamy Viral Protease-Reverse Transcriptase.Journal of virology · 2021Article
- Exploring New Scaffolds for the Dual Inhibition of HIV-1 RT Polymerase and Ribonuclease Associated Functions.Molecules (Basel, Switzerland) · 2021Article
- Analysis and Molecular Determinants of HIV RNase H Cleavage Specificity at the PPT/U3 Junction.Viruses · 2021Article
- HIV-1 Reverse Transcriptase/Integrase Dual Inhibitors: A Review of Recent Advances and Structure-activity Relationship Studies.Iranian journal of pharmaceutical research : IJPR · 2021Review
- 3,7-Dihydroxytropolones Inhibit Initiation of Hepatitis B Virus Minus-Strand DNA Synthesis.Molecules (Basel, Switzerland) · 2020Article
- Evolving understanding of HIV-1 reverse transcriptase structure, function, inhibition, and resistance.Current opinion in structural biology · 2020Review
- Discovery, synthesis, and optimization of an N-alkoxy indolylacetamide against HIV-1 carrying NNRTI-resistant mutations from the Isatis indigotica root.European journal of medicinal chemistry · 2020Article
- RNA Structural Dynamics As Captured by Molecular Simulations: A Comprehensive Overview.Chemical reviews · 2018Review
- Structure of HIV-1 reverse transcriptase cleaving RNA in an RNA/DNA hybrid.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Mechanism of polypurine tract primer generation by HIV-1 reverse transcriptase.The Journal of biological chemistry · 2018Article
- RNase H sequence preferences influence antisense oligonucleotide efficiency.Nucleic acids research · 2017Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Replication of human immunodeficiency virus 1 (HIV-1) involves conversion of its single-stranded RNA genome to double-stranded DNA, which is integrated into the genome of the host. This conversion is catalyzed by reverse transcriptase (RT), which possesses DNA polymerase and RNase H domains. The available crystal structures suggest that at any given time the RNA/DNA substrate interacts with only one active site of the two domains of HIV-1 RT. Unknown is whether a simultaneous interaction of the substrate with polymerase and RNase H active sites is possible. Therefore, the mechanism of the coordination of the two activities is not fully understood. We performed molecular dynamics simulations to obtain a conformation of the complex in which the unwound RNA/DNA substrate simultaneously interacts with the polymerase and RNase H active sites. When the RNA/DNA hybrid was immobilized at the polymerase active site, RNase H cleavage occurred, experimentally verifying that the substrate can simultaneously interact with both active sites. These findings demonstrate the existence of a transient conformation of the HIV-1 RT substrate complex, which is important for modulating and coordinating the enzymatic activities of HIV-1 RT.
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