Structural Characterization of a Therapeutic Anti-Methamphetamine Antibody Fragment: Oligomerization and Binding of Active Metabolites
Figure 4
Conformational changes upon trimer formation.
(a) CDR H3 loop: A superposition of the Cα atoms of residues Thr H89-Thr H107 in the apo structure (magenta) with the METH bound structure (yellow). Six residues belonging to the CDR H3 loop (Ser H97 to Met H100B) show significant displacements. In the apo crystal, the loop residues take up extended conformations elongating the two anti-parallel β-strands to have a sharp turn connection in the place of a long loop. In the METH-bound structure, the CDR H3 region assumes a more spread out conformation to create the environment for METH binding. (b) The shapes of the binding pockets in the free and the antigen bound states: The left panel (apo form) and the right (METH complex) show identical cross sections. The entrance of the binding pocket is broader in apo structure, compared to the METH complex. Color code: Left panel: heavy chain -magenta and light chain -light pink. Right panel: heavy chain- blue light chain-light blue.