ArticleBiochemistry2010
Efavirenz binding to HIV-1 reverse transcriptase monomers and dimers.
Article in Biochemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 36 citations in OpenAlex.
- Human immunodeficiency virus and antiretroviral therapies exert distinct influences across diverse gut microbiomes.Nature microbiology · 2025Article
- Sequence Diversity and Encoded Enzymatic Differences of Monocistronic L1 ORF2 mRNA Variants in the Aged Normal and Alzheimer's Disease Brain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Biophysical Characterization of p51 and p66 Monomers of HIV-1 Reverse Transcriptase with Their Inhibitors.The protein journal · 2023Article
- Conformational Changes in HIV-1 Reverse Transcriptase that Facilitate Its Maturation.Structure (London, England : 1993) · 2019Article
- Non-nucleoside Reverse Transcriptase Inhibitors Inhibit Reverse Transcriptase through a Mutually Exclusive Interaction with Divalent Cation-dNTP Complexes.Biochemistry · 2019Article
- HIV-1 Reverse Transcriptase: A Metamorphic Protein with Three Stable States.Structure (London, England : 1993) · 2019Review
- The HIV-1 p66 homodimeric RT exhibits different conformations in the binding-competent and -incompetent NNRTI site.Proteins · 2017Article
- NMR structure of the HIV-1 reverse transcriptase thumb subdomain.Journal of biomolecular NMR · 2016Article
- Conformational Plasticity of the NNRTI-Binding Pocket in HIV-1 Reverse Transcriptase: A Fluorine Nuclear Magnetic Resonance Study.Biochemistry · 2016Article
- Unfolding the HIV-1 reverse transcriptase RNase H domain--how to lose a molecular tug-of-war.Nucleic acids research · 2016Article
- Article
- Towards structural systems pharmacology to study complex diseases and personalized medicine.PLoS computational biology · 2014Review
- Selective unfolding of one Ribonuclease H domain of HIV reverse transcriptase is linked to homodimer formation.Nucleic acids research · 2014Article
- Biophysical Insights into the Inhibitory Mechanism of Non-Nucleoside HIV-1 Reverse Transcriptase Inhibitors.Biomolecules · 2013Article
- The interplay of structure and dynamics: insights from a survey of HIV-1 reverse transcriptase crystal structures.Proteins · 2013Article
- Article
- Allosteric suppression of HIV-1 reverse transcriptase structural dynamics upon inhibitor binding.Biophysical journal · 2011Article
- Efavirenz binding site in HIV-1 reverse transcriptase monomers.Biochemistry · 2010Article
- Selective killing of human immunodeficiency virus infected cells by non-nucleoside reverse transcriptase inhibitor-induced activation of HIV protease.Retrovirology · 2010Article
- Drug-target residence time: critical information for lead optimization.Current opinion in chemical biology · 2010Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Efavirenz (EFV) is a nonnucleoside reverse transcriptase inhibitor (NNRTI) of HIV-1 reverse transcriptase (RT) used for the treatment of AIDS. RT is a heterodimer composed of p66 and p51 subunits; p51 is produced from p66 by C-terminal truncation by HIV protease. The monomers can form p66/p66 and p51/p51 homodimers as well as the p66/p51 heterodimer. Dimerization and efavirenz binding are coupled processes. In the crystal structure of the p66/p51-EFV complex, the drug is bound to the p66 subunit. The binding of efavirenz to wild-type and dimerization-defective RT proteins was studied by equilibrium dialysis, tryptophan fluorescence, and native gel electrophoresis. A 1:1 binding stoichiometry was determined for both monomers and homodimers. Equilibrium dissociation constants are approximately 2.5 microM for both p66- and p51-EFV complexes, 250 nM for the p66/p66-EFV complex, and 7 nM for the p51/p51-EFV complex. An equilibrium dissociation constant of 92 nM for the p66/p51-EFV complex was calculated from the thermodynamic linkage between dimerization and inhibitor binding. Binding and unbinding kinetics monitored by fluorescence were slow. Progress curve analyses revealed a one-step, direct binding mechanism with association rate constants k(1) of approximately 13.5 M(-1) s(-1) for monomers and heterodimer and dissociation rate constants k(-1) of approximately 9 x 10(-5) s(-1) for monomers. A conformational selection mechanism is proposed to account for the slow association rate. These results show that efavirenz is a slow, tight-binding inhibitor capable of binding all forms of RT and suggest that the NNRTI binding site in monomers and dimers is similar.
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