Figure 3.

Choosing cysteine, histidine, and methionine residues as cruzain inhibitor binding probes. The distribution of (a) cysteine (yellow balls), (b) histidine (cyan balls), and (c) methionine (orange and magenta balls) residues mapped on the crystal structure of the cruzain-K777 complex (PDB 2OZ2).⁶ The catalytic Gln19 (dark blue), Cys25 (red), and His162 (cyan) residues are indicated by boxes. The putative catalytic residue Asn182 is omitted for clarity. Met68 and Met145 (orange), both located on the surface of the substrate binding pocket, and the relatively unstructured N-terminal region (residues 1-24, brown cartoon), are also indicated. (d) The cruzain active site, represented as a 90° rotation about the horizontal axis with respect to parts (a-c). The positions of the catalytic Gln19 (blue), Cys25 (red), His162 (cyan), and Asn182 (green) amide groups are indicated with balls. Orange balls denote positions of the Met68 and Met145 ε-methyl groups; purple balls denote positions of the Met52 and Met152 ε-methyl groups. A cluster of tryptophan residues (Trp184, dark red; Trp188, brown; and Trp144, pink) connects Met145 and Met152 with His162. Glu208 (light green), which forms a portion of the S2 pocket, is also displayed. The van der Waal surfaces of the tryptophan cluster and Glu208 are indicated by meshes. Surface representation of the cruzain active site with (e) and without (f) the K777 structure. Residue colors are the same as part (d).