Effects of efavirenz binding on the subunit equilibria of HIV-1 reverse transcriptase

Biochemistry
Carl F VeneziaMary D Barkley

Abstract

Recent studies showed that nonnucleoside reverse transcriptase inhibitors (NNRTIs) have variable effects on dimerization of p66 and p51 subunits of HIV-1 reverse transcriptase (RT). Efavirenz, one of three NNRTIs currently used in highly active anti-retroviral therapy, enhances subunit dimerization. Sedimentation equilibrium experiments on each subunit and equimolar mixtures of both subunits were used to measure dissociation constants for the three coupled dimerization reactions of RT in the absence and presence of saturating concentrations of the drug. The dimerization constants of the p51/p51 homodimer, the p66/p66 homodimer, and the p66/p51 heterodimer increased 600-, 50-, and 25-fold, respectively, upon binding of efavirenz. The effects of NNRTIs on RT dimerization are consistent with a thermodynamic linkage between subunit association/dissociation and inhibitor binding. Analysis of crystal structures of the p66/p51 heterodimer reveals that efavirenz binding induces small structural changes at the dimer interface.

References

Mar 7, 2001·European Journal of Biochemistry·J F CabodevillaJ J Martínez-Irujo

❮ Previous
Next ❯

Citations

Nov 15, 2012·Applied Biochemistry and Biotechnology·Atsushi KonishiKiyoshi Yasukawa
Nov 26, 2010·Biochemistry·Valerie A BrazPatrick L Wintrode
Jul 15, 2009·Biochemistry·James M SecklerPatrick L Wintrode
Sep 1, 2009·Biochemistry·Carl F VeneziaMary D Barkley
Dec 31, 2009·Biochemistry·Valerie A BrazMary D Barkley
Nov 26, 2010·Nature Structural & Molecular Biology·Shixin LiuXiaowei Zhuang
Nov 14, 2006·PLoS Pathogens·Anna FigueiredoGilda Tachedjian
Jun 28, 2011·Biophysical Chemistry·James L ColeWalter F Stafford
Feb 24, 2009·Analytical Biochemistry·Valerie A Braz, Kathryn J Howard
Mar 29, 2008·Virus Research·Nicolas Sluis-Cremer, Gilda Tachedjian
Apr 29, 2014·Proteins·Naima G SharafRieko Ishima
Jun 4, 2015·ELife·Xunhai ZhengRobert E London
Dec 31, 2010·Biophysical Journal·James M SecklerPatrick L Wintrode
Aug 17, 2011·The Journal of Infectious Diseases·Roger ParedesUNKNOWN EuroSIDA Study Group
Aug 27, 2014·Molecular & Cellular Proteomics : MCP·Sam LievensJan Tavernier
May 10, 2008·Nature·Elio A AbbondanzieriXiaowei Zhuang
Jul 27, 2010·The American Journal on Addictions·Kevin M GrayHimanshu P Upadhyaya
Nov 20, 2016·Journal of Biomolecular NMR·Naima G SharafAngela M Gronenborn
Aug 16, 2017·The Biochemical Journal·Xunhai ZhengRobert E London
Oct 28, 2008·The Journal of Biological Chemistry·Audrey AgopianGilles Divita
Dec 19, 2020·International Journal of Molecular Sciences·Tatiana V IlinaRieko Ishima
Feb 26, 2010·Biochemistry·Xunhai ZhengRobert E London
Apr 14, 2006·Journal of Medicinal Chemistry·Matthis GeitmannU Helena Danielson

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.