Figure 4.

Model of pore collapse with TEA for the en face and edge-on conformations. (A, left) A bird's eye view of two proposed conformations of the aromatic rings of T449F from the edge-on crystal structure of KcsA with TEAs (Lenaeus et al., 2005) and the en face conformation (Cordero-Morales et al., 2006b; Ahern et al., 2006). (Right) A putative “collapse” of this region during slow inactivation, as each aromatic ring was moved 1.5 Å toward the central axis of the pore. (B) The plot shows the effect of fluorinating the aromatic rings on TEA's contribution to the energetics of collapse. The ab initio calculations were done at the MP2 level. Tri-fluorination had little effect (<0.3 kcal/mol) for the edge-on conformation. Consistent with our experimental data, however, increased fluorination causes a monotonically inhibitory effect of TEA on collapse for the en face conformation, where tri-fluorination increases ΔΔE by 2.5 kcal/mol.