title: Structural basis for bifunctional peptide recognition at human δ-opioid receptor.
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.
authors: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, USA.
authors: Gustavo
authors: G
authors: Fenalti
authors: Department of Physics, Arizona State University, Tempe, Arizona, USA.
authors: Nadia A
authors: NA
authors: Zatsepin
authors: 1] Department of Chemistry, Vrije Universiteit Brussel, Brussels, Belgium. [2] Department of Bioengineering Sciences, Vrije Universiteit Brussel, Brussels, Belgium.
authors: Cecilia
authors: C
authors: Betti
authors: 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.
authors: Patrick
authors: P
authors: Giguere
authors: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, USA.
authors: Gye Won
authors: GW
authors: Han
authors: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, USA.
authors: Andrii
authors: A
authors: Ishchenko
authors: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, USA.
authors: Wei
authors: W
authors: Liu
authors: 1] Department of Chemistry, Vrije Universiteit Brussel, Brussels, Belgium. [2] Department of Bioengineering Sciences, Vrije Universiteit Brussel, Brussels, Belgium.
authors: Karel
authors: K
authors: Guillemyn
authors: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, USA.
authors: Haitao
authors: H
authors: Zhang
authors: Department of Physics, Arizona State University, Tempe, Arizona, USA.
authors: Daniel
authors: D
authors: James
authors: Department of Physics, Arizona State University, Tempe, Arizona, USA.
authors: Dingjie
authors: D
authors: Wang
authors: Department of Physics, Arizona State University, Tempe, Arizona, USA.
authors: Uwe
authors: U
authors: Weierstall
authors: Department of Physics, Arizona State University, Tempe, Arizona, USA.
authors: John C H
authors: JC
authors: Spence
authors: Linac Coherent Light Source, SLAC National Accelerator Laboratory, Menlo Park, California, USA.
authors: Sébastien
authors: S
authors: Boutet
authors: Linac Coherent Light Source, SLAC National Accelerator Laboratory, Menlo Park, California, USA.
authors: Marc
authors: M
authors: Messerschmidt
authors: Linac Coherent Light Source, SLAC National Accelerator Laboratory, Menlo Park, California, USA.
authors: Garth J
authors: GJ
authors: Williams
authors: Center for Free Electron Laser Science, Deutsches Elektronen-Synchrotron (DESY), Hamburg, Germany.
authors: Cornelius
authors: C
authors: Gati
authors: Center for Free Electron Laser Science, Deutsches Elektronen-Synchrotron (DESY), Hamburg, Germany.
authors: Oleksandr M
authors: OM
authors: Yefanov
authors: Center for Free Electron Laser Science, Deutsches Elektronen-Synchrotron (DESY), Hamburg, Germany.
authors: Thomas A
authors: TA
authors: White
authors: 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.
authors: Dominik
authors: D
authors: Oberthuer
authors: 1] Center for Free Electron Laser Science, Deutsches Elektronen-Synchrotron (DESY), Hamburg, Germany. [2] Department of Physics, University of Hamburg, Hamburg, Germany.
authors: Markus
authors: M
authors: Metz
authors: 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.
authors: Chun Hong
authors: CH
authors: Yoon
authors: Center for Free Electron Laser Science, Deutsches Elektronen-Synchrotron (DESY), Hamburg, Germany.
authors: Anton
authors: A
authors: Barty
authors: 1] Center for Free Electron Laser Science, Deutsches Elektronen-Synchrotron (DESY), Hamburg, Germany. [2] Department of Physics, University of Hamburg, Hamburg, Germany.
authors: Henry N
authors: HN
authors: Chapman
authors: 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.
authors: Shibom
authors: S
authors: Basu
authors: 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.
authors: Jesse
authors: 000000025544320X
authors: J
authors: Coe
authors: 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.
authors: Chelsie E
authors: CE
authors: Conrad
authors: 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.
authors: Raimund
authors: R
authors: Fromme
authors: 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.
authors: Petra
authors: P
authors: Fromme
authors: 1] Department of Chemistry, Vrije Universiteit Brussel, Brussels, Belgium. [2] Department of Bioengineering Sciences, Vrije Universiteit Brussel, Brussels, Belgium.
authors: Dirk
authors: D
authors: Tourwé
authors: Laboratory of Chemical Biology and Peptide Research, Clinical Research Institute of Montreal, Montreal, Quebec, Canada.
authors: Peter W
authors: PW
authors: Schiller
authors: 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.
authors: Bryan L
authors: BL
authors: Roth
authors: 1] Department of Chemistry, Vrije Universiteit Brussel, Brussels, Belgium. [2] Department of Bioengineering Sciences, Vrije Universiteit Brussel, Brussels, Belgium.
authors: Steven
authors: S
authors: Ballet
authors: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, USA.
authors: Vsevolod
authors: V
authors: Katritch
authors: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, USA.
authors: Raymond C
authors: RC
authors: Stevens
authors: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, USA.
authors: Vadim
authors: 0000000252653914
authors: V
authors: Cherezov
mesh_terms: D001665:Binding Sites; D018360:Crystallography, X-Ray; D057809:HEK293 Cells; D006801:Humans; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry; D017434:Protein Structure, Tertiary; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors / Q000737:chemistry*; D044005:Tetrahydroisoquinolines / Q000737:chemistry
chemical_list: C121668:2',6'-dimethyltyrosyl-1,2,3,4-tetrahydro-3-isoquinolinecarbonyl-phenylalanyl-phenylalaninamide; D009842:Oligopeptides; D017465:Receptors, Opioid, delta; D044005:Tetrahydroisoquinolines