Site-directed M2 proton channel inhibitors enable synergistic combination therapy for rimantadine-resistant pandemic influenza
Fig 2
Eng195 homology models based upon PDB: 2RLF conductance domain structure.
A. Overlapping structures of original 2RLF structure (green) and Eng195 (E195) homology model (light/dark grey corresponding to TM and C-terminal extension of CD, respectively). B. Docking of compound D into lumenal and peripheral binding site within Eng195 model. C. Alteration of Eng195 structure caused by occupation of position 31 by either serine (gold) or asparagine (pale blue). Left: top-down view showing lumenal orientation of Ser31 versus inter-helical Asn31. Middle and zoom: side view of helical displacement and location of Ser31 versus Asn31 sidechains. D. Docking of Rimantadine and compound D into lumenal (top) or peripheral (bottom) binding sites of Eng195 homology model with either Ser31 (gold) or Asn31 (pale blue).