Fig. 5. Temsavir binding pocket.

a Temsavir in its binding pocket within the CRF01_AE_ T/F100 LMHS SOSIP.664. Cryo-EM density map of temsavir is shown (left panel) and residues lining the pocket shown as sticks (right panel). The LMHS introduced residues are labeled in red and H-bonds as blue dashes. b Superimposition of the temsavir binding pockets formed within CRF01_AE_ T/F100 LMHS SOSIP.664 (gray) and BG505-SOSIP.664. The inhibitor molecules are shown in ball-and-sticks while the pocket residues are shown in sticks with or without surface. The LMHS mutations within the pockets are highlighted in red. To the right and left are close-up views into the part of the pocket accommodating the acetyl-phenyl and methyltriazole moiety of the inhibitor, respectively. c The residue-resolved buried-surface-area (BSA) of gp120 contributing to the temsavir-protein interface, as determined by PISA. BSA values represent the average of the three copies in the trimer. The conservation of residues lining the temsavir pocket is shown at the bottom. The height of the residue at each position is proportional to its frequency of distribution among the HIV-1 isolates, as deposited in the Los Alamos HIV database (all clades are included). Residues are colored according to hydrophobicity: black - hydrophobic, green - neutral, blue - hydrophilic. d Close-up views of the extended tails on the thiazole ring from the two temsavir analogues whose structures have been determined (PDB: 6MU6 and 6MU7)¹⁴.