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Figure 4.
Figure 4. Mechanism of TEA blockade. (a) The selectivity
filter in high potassium (PDB entry 1K4C) is shown. In cesium
(PDB entry 1R3L), an additional ion-binding site is observed in
the cavity32 and a cesium ion is shown as a yellow sphere at
this position. Two TEA molecules are shown in the TBA and TEAs
positions, respectively. Arrows point to the external
dehydration transition site observed in potassium and to the
internal dehydration transition site observed in cesium. (b)
Model of blockade. The selectivity filter is shown schematically
with thallium ions drawn as filled circles and TEA as open
circles. Binding of TEA stabilizes the close ion and
destabilizes the remote ion. The observed states are
highlighted. In the case of internal TEA binding, the external
pore collapses to form the proposed inactivated state. (c)
Stereo view down the four-fold axis onto the external TEA site.
Four TEA molecules and their ligands were extracted from CPS
(PDB entry 1A9X) and superimposed by least-squares fitting the
TEA molecules. All possible orientations of the TEA-ligand cloud
were generated and docked into the TEAs structure by a
least-squares fit of the CPS TEA to TEAs. Oxygen ligands of TEA
are red, nitrogen ligands are blue and chloride ions are green.
KcsA residues of the external pore are shown. Arrows identify
carbonyl oxygen atoms and the van der Waals contact between TEA
and Tyr82. (d) View up the symmetry axis onto the internal TEA
site. The same TEA-ligand structure as in c was docked into the
TBA structure by a least-squares fit. Arrows identify carbonyl
and hydroxyl oxygen atoms.
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