HIV-1 Reverse Transcriptase in Complex with Nevirapine: Difference between revisions

Although nonnucleoside RT inhibitors are structurally diverse compounds, they all bind RT in the same location - <scene name='HIV-1_Reverse_Transcriptase_in_Complex_with_Nevirapine/Nnrti_binding_pocket/2'>the NNRTI hydrophobic binding pocket</scene>. The pocket is located in the palm domain of the p66 subunit between the β6-β10-β9 and β12-β13-β14 sheets approximately 10 angstroms from the three catalytic asp residues that make up the polymerase active site.<ref>PMID:1377403</ref> The NNRTI BP is mostly hydrophobic in nature with considerable aromatic residues (Y181, Y188, F227, W229, and Y232), but also contains several hydrophilic residues (K101, K103, S105, D192, and E224 of the p66 subunit and E138 of the β7-β8 loop of the p51 subunit). NNRTIs most likely access the binding pocket at the p66/p51 heterodimer interface surrounded by residues L100, K101, K103, V179, and Y181 of the p66 subunit and E138 of the p51 subunit. These residues are colored tan in the binding pocket scene. <ref>PMID:8805568</ref> Actually, in the absence of ligand, the side chains of Y181 and Y188 point into the core, so the binding pocket doesn't exist in the free enzyme. The binding of NNRTI to HIV RT causes these side chains to shift away and make room for the ligand to enter the binding pocket.<ref>PMID:8805568</ref>