NNRTI resistance can be caused by mutations in the RT p51 subunit, far from the active site

What is it about?

Some rare mutations in HIV-1 reverse transcriptase (RT) associated with NNRTI resistance were identified and characterized. Specifically, these mutations included I132M and I135M. The RT enzyme has two subunits: the p66 subunit that contains the polymerase and RNaseH enzymatic activities and the p51 subunit which is thought to be mainly structural. The p51 subunit is formed by cleavage of the p66 subunit, so most mutations in p66 will also be in p51. While most RT mutations that cause drug resistance are in the p66 subunit where the enzymatic activities are located, the effect of these new mutations surprisingly came from the p51 subunit of RT.

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