HIV-1 Reverse Transcriptase in Complex with Nevirapine

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Introduction

is a viral encoded enzyme that converts the viral single-stranded RNA genome into a double-stranded DNA provirus that is integrated into the host chromosome in the host cell's nucleus. The process of converting viral ssRNA into dsDNA that can incorporate into the host chromosome is called retrotranscription, and is characteristic of all retroviruses. HIV-1 reverse transcriptase is encoded by the human immunodeficiency virus, well known as the etiological agent of acquired immune deficiency syndrome (AIDS).

RT performs three catalytic steps: 1) RNA-dependent DNA polymerization to create a negative sense DNA strand that complements the positive sense viral RNA genome, 2) ribonuclease H cleavage of RNA in the RNA:DNA heteroduplex, and 3) DNA-dependent DNA polymerization to make a dsDNA using the previously synthesized negative sense DNA strand as a template. The dsDNA is transported to the nucleus where it integrates into the host cell's chromosome. HIV-1 is chronic and requires lifelong treatment with a combination of at least three different antiviral drugs. In addition, the emergence of drug-resistant HIV-1 strains means drugs with new viral targets are constantly being developed.

Crystal Structure of HIV-1 Reverse Transcriptase with DNA and the nonnucleoside inhibitor nevirapine (PDB entry 3v81)

Proteopedia Page Contributors and Editors (what is this?)

Madeline Evancie, Michal Harel

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