ArticleJournal of virology2001
YADD mutants of human immunodeficiency virus type 1 and Moloney murine leukemia virus reverse transcriptase are resistant to lamivudine triphosphate (3TCTP) in vitro.
Article in Journal of virology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 32 citations in OpenAlex.
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- Mutations in the SARS-CoV-2 RNA-dependent RNA polymerase confer resistance to remdesivir by distinct mechanisms.Science translational medicine · 2022Article
- 5-methylcytosine-sensitive variants of Thermococcus kodakaraensis DNA polymerase.Nucleic acids research · 2016Article
- Discovery of drugs that possess activity against feline leukemia virus.The Journal of general virology · 2012Article
- Activity of a novel combined antiretroviral therapy of gemcitabine and decitabine in a mouse model for HIV-1.Antimicrobial agents and chemotherapy · 2012Article
- Susceptibility of the human retrovirus XMRV to antiretroviral inhibitors.Retrovirology · 2010Article
- Reverse transcriptase in motion: conformational dynamics of enzyme-substrate interactions.Biochimica et biophysica acta · 2010Review
- Article
- Apparent defects in processive DNA synthesis, strand transfer, and primer elongation of Met-184 mutants of HIV-1 reverse transcriptase derive solely from a dNTP utilization defect.The Journal of biological chemistry · 2008Article
- Characterization of the polymerase and RNase H activities of human foamy virus reverse transcriptase.Journal of virology · 2004Article
- Molecular impact of the M184V mutation in human immunodeficiency virus type 1 reverse transcriptase.Antimicrobial agents and chemotherapy · 2003Review
- A conformationally locked analogue of the anti-HIV agent stavudine. An important correlation between pseudorotation and maximum amplitude.Journal of medicinal chemistry · 2003Article
- Effect of lamivudine on transmission of human T-cell lymphotropic virus type 1 to adult peripheral blood mononuclear cells in vitro.Antimicrobial agents and chemotherapy · 2002Article
- Nucleoside analog resistance caused by insertions in the fingers of human immunodeficiency virus type 1 reverse transcriptase involves ATP-mediated excision.Journal of virology · 2002Article
- Mutation of the catalytic domain of the foamy virus reverse transcriptase leads to loss of processivity and infectivity.Journal of virology · 2002Article
- The M184V mutation reduces the selective excision of zidovudine 5'-monophosphate (AZTMP) by the reverse transcriptase of human immunodeficiency virus type 1.Journal of virology · 2002Article
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
When human immunodeficiency virus type 1 (HIV-1) is selected for resistance to 3TC, the methionine normally present at position 184 is replaced by valine or isoleucine. Position 184 is the X of the conserved YXDD motif; positions 185 and 186 form part of the triad of aspartic acids at the polymerase active site. Structural and biochemical analysis of 3TC-resistant HIV-1 reverse transcriptase (RT) led to a model in which a beta-branched amino acid at position 184 would act as a steric gate. Normal deoxynucleoside triphosphates (dNTPs) could still be incorporated; the oxathiolane ring of 3TCTP would clash with the beta branch of the amino acid at position 184. This model can also explain 3TC resistance in feline immunodeficiency virus and human hepatitis B virus. However, it has been reported (14) that murine leukemia viruses (MLVs) with valine (the amino acid present in the wild type), isoleucine, alanine, serine, or methionine at the X position of the YXDD motif are all resistant to 3TC. We prepared purified wild-type MLV RT and mutant MLV RTs with methionine, isoleucine, and alanine at the X position. The behavior of these RTs was compared to those of wild-type HIV-1 RT and of HIV-1 RT with alanine at the X position. If alanine is present at the X position, both MLV RT and HIV-1 RT are relatively resistant to 3TCTP in vitro. However, the mutant enzymes were impaired relative to their wild-type counterparts; there appears to be steric hindrance for both 3TCTP and normal dNTPs.
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