Figure 10.

Homology modeling of the IKCa. Computer modeling of the IKCa channel using either the closed or open KcsA channel structure as template. Surface and ribbon representations of the open IKCa S5-P-S6 region are illustrated in B and C, respectively. B also includes a surface representation of a single S6 segment for the open channel. The molecular surface computed for the closed IKCa S5-P-S6 region is presented in A. According to the proposed models, the residues V275, T278, and V282 are lining the pore lumen resulting in a cavity 10 Å wide at the level of V275. Also, the endogenous cysteines (yellow in Fig. 9 C) at positions 269, 276, and 277 are presented as facing opposite to the pore lumen, whereas the C267 residue is predicted to be oriented toward the selectivity filter. A color representation of the MTSET modification rate for channel inhibition and/or activation is superimposed on the closed and open IKCa channel structures. Residues with slow (<5 M⁻¹s⁻¹), intermediate (5 M⁻¹s⁻¹ to 20 M⁻¹s⁻¹), and fast (>50 M⁻¹s⁻¹) rates of modification are colored in blue, orange, and red respectively. The pore lining residue A286 is seen as being the most accessible (red), whereas residues with the slowest rates of modification (blue) turned out to be located either inside (T278) or opposite to the pore lumen (V285). B also illustrates that all the residues from A283 to A286 are accessible to MTSET irrespective of their orientation relative to the pore central axis. (D) Cross-section area for residues 264–292 computed for the open and closed IKCa structures. Z refers to the channel axial distance with Z = 0 at V275. The closed channel structure predicts a central cavity extending from residues 272–278. The cross-section area for residues spanning the 282–286 region appeared under these conditions too small to accommodate an MTSET molecule of 5.8 Å diameter assuming a rigid structure for IKCa. A flexible structure extending below V282 can, however, account for the SCAM results.