Structural basis for bifunctional peptide recognition at human δ-opioid receptor

Gustavo Fenalti, Nadia A. Zatsepin, Cecilia Betti, Patrick Giguere, Gye Won Han, Andrii Ishchenko, Wei Liu, Karel Guillemyn, Haitao Zhang, Daniel James, Dingjie Wang, Uwe Weierstall, John C.H. Spence, Sébastien Boutet, Marc Messerschmidt, Garth J. Williams, Cornelius Gati, Oleksandr M. Yefanov, Thomas A. White, Dominik OberthuerMarkus Metz, Chun Hong Yoon, Anton Barty, Henry N. Chapman, Shibom Basu, Jesse Coe, Chelsie E. Conrad, Raimund Fromme, Petra Fromme, Dirk Tourwé, Peter W. Schiller, Bryan L. Roth, Steven Ballet, Vsevolod Katritch, Raymond C. Stevens, Vadim Cherezov

Research output: Contribution to journalArticlepeer-review

109 Citations (Scopus)


Bifunctional μ- and δ-opioid receptor (OR) ligands are potential therapeutic alternatives, with diminished side effects, to alkaloid opiate analgesics. We solved the structure of human δ-OR bound to the bifunctional δ-OR antagonist and μ-OR agonist tetrapeptide H-Dmt-Tic-Phe-Phe-NH 2 (DIPP-NH 2) by serial femtosecond crystallography, revealing a cis-peptide bond between H-Dmt and Tic. The observed receptor-peptide interactions are critical for understanding of the pharmacological profiles of opioid peptides and for development of improved analgesics.

Original languageEnglish
Pages (from-to)265-268
Number of pages4
JournalNature Structural and Molecular Biology
Issue number3
Publication statusPublished - Mar 6 2015

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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