Conformational changes in HIV-1 reverse transcriptase induced by nonnucleoside reverse transcriptase inhibitor binding.
Nonnucleoside reverse transcriptase inhibitors (NNRTI) are a group of small hydrophobic compounds with diverse structures that specifically inhibit HIV-1 reverse transcriptase (RT). NNRTIs interact with HIV-1 RT by binding to a single site on the p66 subunit of the p66/p51 heterodimeric enzyme, termed the NNRTI-binding pocket (NNRTI-BP). This binding interaction results in both short-range and long-range distortions of RT structure. In this article, we review the structural, computational and experimental evidence of the NNRTI-induced conformational changes in HIV-1 RT and relate them to the mechanism by which these compounds inhibit HIV-1 reverse transcription.
Sluis-Cremer
Nicolas
N
University of Pittsburgh, Department of Medicine, Division of Infectious Diseases, Pittsburgh, Pennsylvania 15261, USA. CremerN@msx.dept-med.pitt.edu
Temiz
N Alpay
NA
Bahar
Ivet
I
D019380:Anti-HIV Agents / Q000378:metabolism* / Q000494:pharmacology; D001665:Binding Sites; D054303:HIV Reverse Transcriptase / Q000737:chemistry* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation / Q000187:drug effects; D018894:Reverse Transcriptase Inhibitors / Q000378:metabolism* / Q000494:pharmacology
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase