Abstract
HIV-1 Reverse Transcriptase (HIV-1 RT) has been the target of numerous approved anti-AIDS drugs that are key components of Highly Active Anti-Retroviral Therapies (HAART). It remains the target of extensive structural studies that continue unabated for almost twenty years. The crystal structures of wild-type or drug-resistant mutant HIV RTs in the unliganded form or in complex with substrates and/or drugs have offered valuable glimpses into the enzyme’s folding and its interactions with DNA and dNTP substrates, as well as with nucleos(t)ide reverse transcriptase inhibitor (NRTI) and non-nucleoside reverse transcriptase inhibitor (NNRTIs) drugs. These studies have been used to interpret a large body of biochemical results and have paved the way for innovative biochemical experiments designed to elucidate the mechanisms of catalysis and drug inhibition of polymerase and RNase H functions of RT. In turn, the combined use of structural biology and biochemical approaches has led to the discovery of novel mechanisms of drug resistance and has contributed to the design of new drugs with improved potency and ability to suppress multi-drug resistant strains.
Highlights
The reverse transcription of the viral single-stranded (+) RNA genome into double-stranded DNA is an essential step in the replication of HIV
A key missing structure of reverse transcriptase (RT) complexed with template-primer, dNTP, and non-nucleoside reverse transcriptase inhibitor (NNRTIs) would elucidate the structural changes that NNRTIs cause to the catalytic complex
In this review we examine briefly the contribution of structural information in the elucidation of the mechanisms of RT resistance to nucleos(t)ide reverse transcriptase inhibitor (NRTI) and NNRTIs
Summary
The reverse transcription of the viral single-stranded (+) RNA genome into double-stranded DNA (dsDNA) is an essential step in the replication of HIV. The human immunodeficiency virus type I reverse transcriptase (HIV-1 RT) has two distinct activities: (i) a DNA polymerase activity, which uses either RNA or DNA as template and (ii) an RNase H activity, which degrades. The p66 subunit is 560 amino acids long and contains the active sites of the polymerase and RNase H functions of the enzyme; the p51 subunit contains the first 440 amino acids of p66 and is derived from HIV-1 protease-mediated cleavage of the RNase H domain from the p66 subunit [3]. HIV-1 RT functions as heterodimer of p66 and p51 subunits.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
