Structural basis for bifunctional peptide recognition at human δ-opioid receptor Academic Article uri icon

abstract

  • 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-NH2 (DIPP-NH2) 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.

authors

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

publication date

  • 2015