FIGURE 4.

The back door region in Fab410-bound BfAChE and comparison with other AChEs. A, overall view of the Fab410-BfAChE complex (one subunit only) slightly rotated from Fig. 3A (top subunit) to better show the solvent-accessible paths in BfAChE. The lining walls of the active site gorge and back door channel are shown as transparent green and red surfaces, and their pathways are shown as green and red center lines, respectively (other color codes are as in Fig. 3A). B, omit electron density maps contoured at 3.0σ of the back door region in BfAChE showing the two equally represented alternate conformations of Tyr⁴⁴² and their respective interactions with neighboring residues stabilized by H-bonds (dashed lines). C, close-up views of the continued path from the PAS at the gorge entrance to the back door region in BfAChE (left), TcAChE (center) (PDB code 2XI4) and DmAChE (right) (PDB code 1DX4) in the same orientation with green and red lining walls for the active site gorge and back door channel (see A). BfAChE and TcAChE Tyr⁴⁴² in the rotated conformation and DmAChE Asp⁴⁸² are displayed in pink, whereas BfAChE and TcAChE Tyr⁴⁴² in the usual conformation are in white. Key side chains from the long Ω loop are in brown, and those lining the channel are in yellow for BfAChE, light orange for TcAChE, and green for DmAChE. In BfAChE and TcAChE, Tyr⁴⁴² in the rotated conformation points toward a neighboring hydrophobic pocket and leaves the back door channel open, whereas in DmAChE, Asp⁴⁸² is too small to occlude the channel. D, profiles of the back door channel in BfAChE (red line), TcAChE (orange line), and DmAChE (brown line) and of the gorge path in BfAChE up the constricted region midway in the gorge (green line) as calculated by CAVER. (The dotted line denotes the gorge path between the constricted region and the gorge entrance that was ignored by the program.)