Fig. 4: NNRTI inhibition of the RTIC. | Nature Communications

Fig. 4: NNRTI inhibition of the RTIC.

From: High-resolution view of HIV-1 reverse transcriptase initiation complexes and inhibition by NNRTI drugs

Fig. 4

a miniRTIC–EFZ NNRTI-binding pocket. EFZ N1 atom forms a hydrogen bond (black dashed line) with the oxygen atom on the backbone of K101. Corresponding EFZ density in mesh from 2.9-Å EM map. Y181 and Y188 flip toward the polymerase-active site to accommodate the drug. b miniRTIC–NVP NNRTI-binding pocket. Corresponding NVP density in mesh from 3.1-Å EM map. Similar to a, Y181 and Y188 flip to accommodate the drug. c Superposed binding pocket of miniRTIC–NVP (green) and RT–DNA–NVP (pink, 3V81 [https://doi.org/10.2210/pdb3v81/pdb]) after alignment on palm domain backbone residues (“Methods”). d Superposed apo-miniRTIC (purple), miniRTIC–EFZ (beige), and miniRTIC–NVP (green) after alignment on palm domain backbone residues (“Methods”). NNRTI binding locks the primer grip, causing the thumb to hyperextend by ~2 Å. e NNRTI binding causes compaction of the primer grip by ~2 Å to assist in the hydrophobic packing of the drug. The primer grips of both miniRTIC–NVP (green) and miniRTIC–EFZ (beige) exhibit similar compaction motions in reference to apo-miniRTIC (purple).

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