Figure 9.

Structure of the human ARG2/C0021158 Fab binding interface and Fab-induced changes within ARG2’s active site. (a) Side view of the binding interface between C0021158 Fab and ARG2, with interacting side chains shown as sticks. Key active site residues involved in antibody-induced inhibition (Arg39, Asn158 and His160) are also shown as sticks for clarity. The Fab (V_H/C_H in orange and V_L/C_L in light orange, CDRs in yellow and light yellow for V_H and V_L, respectively) is shown as a cartoon inside a semi-opaque surface representation. ARG2 is shown as blue cartoon, with the region undergoing conformational change upon binding shown in dark purple, manganese ions shown as purple spheres and sulfate shown as sticks. (b) Close-up top-down view of the hydrophobic cleft between V_H and V_L and the central single-turn helix of the epitope on ARG2. (c) A close-up of the ARG2 active site when bound to C0021158 Fab (blue, with conformational changes upon binding in dark purple) superimposed with free ARG2 bound to an inhibitor (light gray, PDB-ID 4HZE²⁸). Critical catalytic and coordinating side chains are shown as sticks. (d) Electron density map (2F_o – F_c, contoured at 2.0 σ (gray mesh) for regions of ARG2 within 2.0 Å of highlighted residues and ligands at the active site of ARG2 when bound to C0021158. Complexation of the dimanganese center and other interactions of interest are shown with black dashes.