Fig. 5.

CypD X-ray structure in complex with the amide derivative 40 (PDB-ID: 6R8W) at 1.4 Å resolution, which was derived from fragment linking of 3 and 7. The bicyclic ring of 3 is bound in the S2 pocket with specific H-bonds involving also water molecules 1 and 2. The bicyclic norbornane maleimide ring of fragment 7 binds in two alternative conformations (green and yellow) distinguished by 180° rotation in the S1′ pocket. In both orientations, the maleimide carbonyl O-atom is in H-bond contact to Asn144 and His168. The amide group connecting both fragments forms H-bonds to Arg97 (direct) and Gln116 and His (water mediated).