Figure 5.

Comparison of bound and unbound structures indicate conformational changes during eptinezumab binding to CGRP. Eptinezumab is in yellow. The CDRs are colored using PyMOL color names, where light-chain regions are in shades of green (L1 [pale green], L2 [lemon], L3 [lime]) and heavy-chain regions are in shades of blue (H1 [light blue], H2 [marine], H3 [blue]). Superposed structure using the FV domain as template a) of the unbound (translucent) and bound (opaque) structure. CDR H3 (blue) clearly goes through a structural reorganization where an internal H-bond between Asp99 and Arg97 in the bound form goes to an H-bond between Asp99 and light chain Lys46 inducing a movement of Asp99 CA by ~3 Å (from 2.5 Å to 3.5 Å following the alignment); b) of the unbound (translucent) and bound (opaque). Asn54 rotates and makes a direct contact with CGRP Asn113. Although the angles between both amides is not right for a proper hydrogen bond, the inter distance between N-Asn113 and O from Asn54 CDR H2 is 2.8 Å