Format

Send to

Choose Destination
Nat Struct Mol Biol. 2015 Mar;22(3):265-8. doi: 10.1038/nsmb.2965. Epub 2015 Feb 16.

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

Author information

1
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, USA.
2
Department of Physics, Arizona State University, Tempe, Arizona, USA.
3
1] Department of Chemistry, Vrije Universiteit Brussel, Brussels, Belgium. [2] Department of Bioengineering Sciences, Vrije Universiteit Brussel, Brussels, Belgium.
4
1] National Institute of Mental Health Psychoactive Drug Screening Program, University of North Carolina Chapel Hill Medical School, Chapel Hill, North Carolina, USA. [2] Department of Pharmacology, University of North Carolina Chapel Hill Medical School, Chapel Hill, North Carolina, USA. [3] Division of Chemical Biology and Medicinal Chemistry, University of North Carolina Chapel Hill Medical School, Chapel Hill, North Carolina, USA.
5
Linac Coherent Light Source, SLAC National Accelerator Laboratory, Menlo Park, California, USA.
6
Center for Free Electron Laser Science, Deutsches Elektronen-Synchrotron (DESY), Hamburg, Germany.
7
1] Center for Free Electron Laser Science, Deutsches Elektronen-Synchrotron (DESY), Hamburg, Germany. [2] Institute of Biochemistry and Molecular Biology, University of Hamburg, Hamburg, Germany.
8
1] Center for Free Electron Laser Science, Deutsches Elektronen-Synchrotron (DESY), Hamburg, Germany. [2] Department of Physics, University of Hamburg, Hamburg, Germany.
9
1] Center for Free Electron Laser Science, Deutsches Elektronen-Synchrotron (DESY), Hamburg, Germany. [2] European X-ray Free-Electron Laser Facility (XFEL GmbH), Hamburg, Germany.
10
1] Department of Chemistry and Biochemistry, Arizona State University, Tempe, Arizona, USA. [2] Center for Applied Structural Discovery at the Biodesign Institute, Arizona State University, Tempe, Arizona, USA.
11
Laboratory of Chemical Biology and Peptide Research, Clinical Research Institute of Montreal, Montreal, Quebec, Canada.

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-NH2 (DIPP-NH2) 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.

PMID:
25686086
PMCID:
PMC4351130
DOI:
10.1038/nsmb.2965
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center