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

Gustavo Fenalti, Nadia Zatsepin, Cecilia Betti, Patrick Giguere, Gye Won Han, Andrii Ishchenko, Wei Liu, Karel Guillemyn, Haitao Zhang, Daniel James, Dingjie Wang, Uwe Weierstall, John 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

    Research output: Contribution to journalArticle

    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 languageEnglish (US)
    Pages (from-to)265-268
    Number of pages4
    JournalNature Structural and Molecular Biology
    Volume22
    Issue number3
    DOIs
    StatePublished - 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

    Structural basis for bifunctional peptide recognition at human δ-opioid receptor. / Fenalti, Gustavo; Zatsepin, Nadia; Betti, Cecilia; Giguere, Patrick; Han, Gye Won; Ishchenko, Andrii; Liu, Wei; Guillemyn, Karel; Zhang, Haitao; James, Daniel; Wang, Dingjie; Weierstall, Uwe; Spence, John; 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 journalArticle

    Fenalti, G, Zatsepin, N, Betti, C, Giguere, P, Han, GW, Ishchenko, A, Liu, W, Guillemyn, K, Zhang, H, James, D, Wang, D, Weierstall, U, Spence, J, 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, Gustavo ; Zatsepin, Nadia ; Betti, Cecilia ; Giguere, Patrick ; Han, Gye Won ; Ishchenko, Andrii ; Liu, Wei ; Guillemyn, Karel ; Zhang, Haitao ; James, Daniel ; Wang, Dingjie ; Weierstall, Uwe ; Spence, John ; 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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