Fig. 2. Molecular signatures of nalfurafine-bound KOR.

a Alignment of the antagonist JDTic, agonist MP1104, and nalfurafine in the binding pocket of KOR. b The residue E209^ECL2 forms a lid on the top of nalfurafine. c The interaction between the cyclopropyl methyl group of nalfurafine and hydrophobic pocket residues. d The furan ring of nalfurafine forms unique interaction with the ‘triad’ pocket including F114^2.59/W124^ECL1/V134^3.28. e Mutagenesis studies confirm the role of residues that interact with nalfurafine. Data are expressed as the mean ± SEM of three independent experiments (n = 3 experiments each done in duplicate) and summarized from curves attached in Supplemental Figs. 1–3. Values in each plot were summarized in Supplemental Tables 3–5.