Himmel,D., Sarafianos, S., Dharmasena, S., Hossain, M., McCoy-Simandle, K., Ilina, T., Clark, A., Knight, J., Julias, J., and et al. HIV-1 Reverse Transcriptase Structure with RNase H Inhibitor dihydroxy benzoyl naphthyl Hydrazone Bound at a Novel Site. United States: N. p., 2007.
Web.
Himmel,D., Sarafianos, S., Dharmasena, S., Hossain, M., McCoy-Simandle, K., Ilina, T., Clark, A., Knight, J., Julias, J., & et al. HIV-1 Reverse Transcriptase Structure with RNase H Inhibitor dihydroxy benzoyl naphthyl Hydrazone Bound at a Novel Site. United States.
Himmel,D., Sarafianos, S., Dharmasena, S., Hossain, M., McCoy-Simandle, K., Ilina, T., Clark, A., Knight, J., Julias, J., and et al. Mon .
"HIV-1 Reverse Transcriptase Structure with RNase H Inhibitor dihydroxy benzoyl naphthyl Hydrazone Bound at a Novel Site". United States.
doi:.
@article{osti_930398,
title = {HIV-1 Reverse Transcriptase Structure with RNase H Inhibitor dihydroxy benzoyl naphthyl Hydrazone Bound at a Novel Site},
author = {Himmel,D. and Sarafianos, S. and Dharmasena, S. and Hossain, M. and McCoy-Simandle, K. and Ilina, T. and Clark, A. and Knight, J. and Julias, J. and et al.},
abstractNote = {The rapid emergence of drug-resistant variants of human immunodeficiency virus, type 1 (HIV-1), has limited the efficacy of anti-acquired immune deficiency syndrome (AIDS) treatments, and new lead compounds that target novel binding sites are needed. We have determined the 3.15 {angstrom} resolution crystal structure of HIV-1 reverse transcriptase (RT) complexed with dihydroxy benzoyl naphthyl hydrazone (DHBNH), an HIV-1 RT RNase H (RNH) inhibitor (RNHI). DHBNH is effective against a variety of drug-resistant HIV-1 RT mutants. While DHBNH has little effect on most aspects of RT-catalyzed DNA synthesis, at relatively high concentrations it does inhibit the initiation of RNA-primed DNA synthesis. Although primarily an RNHI, DHBNH binds >50 {angstrom} away from the RNH active site, at a novel site near both the polymerase active site and the non-nucleoside RT inhibitor (NNRTI) binding pocket. When DHBNH binds, both Tyr181 and Tyr188 remain in the conformations seen in unliganded HIV-1 RT. DHBNH interacts with conserved residues (Asp186, Trp229) and has substantial interactions with the backbones of several less well-conserved residues. On the basis of this structure, we designed substituted DHBNH derivatives that interact with the NNRTI-binding pocket. These compounds inhibit both the polymerase and RNH activities of RT.},
doi = {},
journal = {ACS Chemical Biology},
number = ,
volume = 1,
place = {United States},
year = {Mon Jan 01 00:00:00 EST 2007},
month = {Mon Jan 01 00:00:00 EST 2007}
}
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