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Updated: Apr 21, 2026

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance
Scott J Garforth1, Chisanga Lwatula1, Vinayaka R Prasad2
1Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. scott.garforth@einstein.yu.edu.
Abstract:
Mutations in HIV-1 reverse transcriptase (RT) that confer nucleoside analog RT inhibitor resistance have highlighted the functional importance of several active site residues (M184, Q151 and K65) in RT catalytic function. Of these, K65 residue is notable due to its pivotal position in the dNTP-binding pocket, its involvement in nucleoside analog resistance and polymerase fidelity. This review focuses on K65 residue and summarizes a substantial body of biochemical and structural studies of its role in RT function and the functional consequences of the K65R mutation.
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