Figure 4.
Binding of spiro-adamantyl amine to the Inwardclosed state. Hydrogen bonds are shown as yellow dashes. (a, b) Side views of the amantadine-bound Inwardclosed M2 structure (a, 6BKK, cyan, monomers B and D) and the spiro-adamantyl amine-bound Inwardclosed M2 structure (b, 6BMZ, yellow, monomers B and D). The spiro-adamantyl amine inhibitor binds with its ammonium group deeper in the channel. The Ala30 water layer (red) is completely displaced, and the inhibitor ammonium group is within hydrogen-bonding distance of the Gly34 water layer (purple). (c) Chemical structures of spiro-adamantyl amine (top) and amantadine (bottom) showing the adamantyl C2 and C3 symmetry axes.