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

Bi-functional μ- and δ- opioid receptor (OR) ligands are potential therapeutic alternatives to alkaloid opiate analgesics with diminished side effects. We solved the structure of human δ-OR bound to the bi-functional δ-OR antagonist and μ-OR agonist tetrapeptide H-Dmt(1)-Tic(2)-Phe(3)-Phe(4)-NH(2) (...

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Detalles Bibliográficos
Autores principales: 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 C.H., 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2015
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4351130/
https://www.ncbi.nlm.nih.gov/pubmed/25686086
http://dx.doi.org/10.1038/nsmb.2965
Descripción
Sumario:Bi-functional μ- and δ- opioid receptor (OR) ligands are potential therapeutic alternatives to alkaloid opiate analgesics with diminished side effects. We solved the structure of human δ-OR bound to the bi-functional δ-OR antagonist and μ-OR agonist tetrapeptide H-Dmt(1)-Tic(2)-Phe(3)-Phe(4)-NH(2) (DIPP-NH(2)) by serial femtosecond crystallography, revealing a cis-peptide bond between H-Dmt(1) and Tic(2). The observed receptor-peptide interactions are critical to understand the pharmacological profiles of opioid peptides, and to develop improved analgesics.

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