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

doi:10.1038/nsmb.2965

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

Journal Article · 16 February 2015 · Nature Structural & Molecular Biology

DOI: https://doi.org/10.1038/nsmb.2965 · OSTI ID:2530157

Fenalti, Gustavo ^[1]; Zatsepin, Nadia A. ^[2]; Betti, Cecilia ^[3]; Giguere, Patrick ^[4]; Han, Gye Won ^[1]; Ishchenko, Andrii ^[1]; Liu, Wei ^[1]; Guillemyn, Karel ^[3]; Zhang, Haitao ^[1]; James, Daniel ^[2]; Wang, Dingjie ^[2]; Weierstall, Uwe ^[2]; Spence, John C. H. ^[2]; Boutet, Sébastien ^[5]; Messerschmidt, Marc ^[5]; Williams, Garth J. ^[5]; Gati, Cornelius ^[6]; Yefanov, Oleksandr M. ^[6]; White, Thomas A. ^[6]; Oberthuer, Dominik ^[7] more »

The Scripps Research Inst., La Jolla, CA (United States)
Arizona State Univ., Tempe, AZ (United States)
Vrije Universiteit Brussel (VUB), Brussels (Belgium)
University of North Carolina, Chapel Hill, NC (United States)
SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States). Linac Coherent Light Source (LCLS)
Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)
Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Univ. of Hamburg (Germany)
Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); European X-ray Free-Electron Laser (XFEL), Hamburg (Germany)
Clinical Research Institute of Montreal, QC (Canada)

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. Finally, the observed receptor-peptide interactions are critical for understanding of the pharmacological profiles of opioid peptides and for development of improved analgesics.

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Research Organization:: SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States); Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES); National Institutes of Health (NIH)

Contributing Organization:: Argonne National Laboratory (ANL)

Grant/Contract Number:: AC02-76SF00515; U54 GM094618; R01 GM108635; R01 GM095583; DA-004443; Y1-CO-1020

OSTI ID:: 2530157

Alternate ID(s):: OSTI ID: 1178834

Journal Information:: Nature Structural & Molecular Biology, Vol. 22, Issue 3; ISSN 1545-9993

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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