Figure 4. Molecular modeling of human AMHR2-ED.

Proposed binding sites for the cognate AMH ligand include the key natural AMH binding site I, ⁴RRTCVFFEAPGV¹⁵ represented in red in (A) the primary amino acid sequence and as a red beta sheet in (B) the ribbon model juxtaposed but antiparallel to the ²⁰KTLGELL²⁶ binding site of the 4D12G1 mAb depicted in blue in both the primary sequence and as a beta sheet in the ribbon model. Another strong AMH binding site II, ³⁴RAIRCLYSR⁴² is represented by a long yellow loop also adjacent to the ²⁰KTLGELL²⁶ binding site of the 4D12G1 mAb. In contrast, the ⁵³DRAQVEM⁵⁹ binding site of the 12G4 mAb and its 3C23K humanized and glyco-engineered variant (a. k. a. GM102) is closer to the weaker tertiary and quaternary AMH binding sites ⁴⁶GIWNL⁵⁰ and ⁸³PSPGSTLFT⁹¹, respectively. Arrows point to the juxtaposition of the blue ²⁰KTLGELL²⁶ binding site of the 4D12G1 mAb with the red AMH I binding site, ⁴RRTCVFFEAPGV¹⁵ and the yellow AMH binding site II ³⁴RAIRCLYSR⁴² in (C) a top view of the ribbon model as well as in (D) a 90° rotational view.