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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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
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author 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
author_facet 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
author_sort Fenalti, Gustavo
collection PubMed
description 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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spelling pubmed-43511302015-09-01 Structural basis for bifunctional peptide recognition at human δ-Opioid receptor 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 Nat Struct Mol Biol Article 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. 2015-02-16 2015-03 /pmc/articles/PMC4351130/ /pubmed/25686086 http://dx.doi.org/10.1038/nsmb.2965 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
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
Structural basis for bifunctional peptide recognition at human δ-Opioid receptor
title Structural basis for bifunctional peptide recognition at human δ-Opioid receptor
title_full Structural basis for bifunctional peptide recognition at human δ-Opioid receptor
title_fullStr Structural basis for bifunctional peptide recognition at human δ-Opioid receptor
title_full_unstemmed Structural basis for bifunctional peptide recognition at human δ-Opioid receptor
title_short Structural basis for bifunctional peptide recognition at human δ-Opioid receptor
title_sort structural basis for bifunctional peptide recognition at human δ-opioid receptor
topic Article
url 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
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