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. 2023 Sep 5;14:5408. doi: 10.1038/s41467-023-41119-7

Fig. 3. Hybridization and the selective state stabilized by 12b.

Fig. 3

a Compound 12b contains the head group of DDD85646, the tail group of IMP-1002, and has a similar topology as IMP-1002. b Compound 12b adopts a similar binding site pose as IMP-1002 but displays an orientational change in its biaryl core. The piperazine group occupies a similar binding site location as that of DDD85646, but the N4 atoms are misaligned, reflecting the similar pose to that of IMP-1002 but difference in spacer lengths. c Misalignment of the piperazine group with that of DDD85646 results in different interactions with nearby polar sites of PvNMT via N4. d Both 12b and IMP-1002 stabilize the S state of Tyr211, but the pyridine moiety of 12b incorporates an additional water molecule, which accompanies the ligand orientational change. Additional conformational differences occur in Tyr211, His213, and Phe226. In panels c, d, aligned residues of IMP-1002- and DDD85646-bound PvNMT are colored black [PDB entries 6MB121 and 2YND20, respectively]. Hydrogen bonding and salt bridge interactions involving 12b are depicted using dashed lines.