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 Oberthuer; Markus 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

doi:10.1038/nsmb.2965

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 Oberthuer & 16 others Markus 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

Arizona State University

Research output: Contribution to journal › Article

83 Citations (Scopus)

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-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 language	English
Pages (from-to)	265-268
Number of pages	4
Journal	Nature Structural and Molecular Biology
Volume	22
Issue number	3
DOIs	https://doi.org/10.1038/nsmb.2965
Publication status	Published - Mar 6 2015

Fingerprint

Opioid Receptors

Peptides

Analgesics

Opiate Alkaloids

phenylalanylphenylalanine

Crystallography

Peptide Receptors

Opioid Peptides

Narcotic Antagonists

Pharmacology

Ligands

2',6'-dimethyltyrosyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid

Therapeutics

ASJC Scopus subject areas

Structural Biology
Molecular Biology

Cite this

Fenalti, G., Zatsepin, N. A., Betti, C., Giguere, P., Han, G. W., Ishchenko, A., ... Cherezov, V. (2015). Structural basis for bifunctional peptide recognition at human δ-opioid receptor. Nature Structural and Molecular Biology, 22(3), 265-268. https://doi.org/10.1038/nsmb.2965

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.

In: Nature Structural and Molecular Biology, Vol. 22, No. 3, 06.03.2015, p. 265-268.

Research output: Contribution to journal › Article

Fenalti, G, Zatsepin, NA, Betti, C, Giguere, P, Han, GW, Ishchenko, A, Liu, W, Guillemyn, K, Zhang, H, James, D, Wang, D, Weierstall, U, Spence, JCH, Boutet, S, Messerschmidt, M, Williams, GJ, Gati, C, Yefanov, OM, White, TA, Oberthuer, D, Metz, M, Yoon, CH, Barty, A, Chapman, HN, Basu, S, Coe, J, Conrad, CE, Fromme, R, Fromme, P, Tourwé, D, Schiller, PW, Roth, BL, Ballet, S, Katritch, V, Stevens, RC & Cherezov, V 2015, 'Structural basis for bifunctional peptide recognition at human δ-opioid receptor', Nature Structural and Molecular Biology, vol. 22, no. 3, pp. 265-268. https://doi.org/10.1038/nsmb.2965

Fenalti G, Zatsepin NA, Betti C, Giguere P, Han GW, Ishchenko A et al. Structural basis for bifunctional peptide recognition at human δ-opioid receptor. Nature Structural and Molecular Biology. 2015 Mar 6;22(3):265-268. https://doi.org/10.1038/nsmb.2965

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. In: Nature Structural and Molecular Biology. 2015 ; Vol. 22, No. 3. pp. 265-268.

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10.1038/nsmb.2965