Figure 4

Representative inhibitors (from Table 1) docked into PpAChE1 (wild type) and superimposed into the G119S (PpAChE position S256) mutant: 4a) propoxur, a phenylcarbamate; 4b) eserine, a cationic carbamate; 4c) pyrazolecarbamate (compound 4), a ‘small core’ carbamate; 4d) tacrine, a non-covalent active site inhibitor; 4e) donepezil, a bivalent inhibitor; 4f) ethidium, a peripheral site inhibitor. Van der Waals surfaces of the inhibitor (green) and mutated serine S256 (PpAChE1 sequence numbering) hydroxyl (red) are shown. Red contour lines delineate the overlap (clash) region (where present). Key residues such as W221 (active site ‘floor’), W417 (peripheral site wall), catalytic serine S336 and histidine H576, as well as sidechains F425 and Y258 most affected by the mutation at G/S256 are shown in ball-and-stick representation.