Elucidating the active δ-opioid receptor crystal structure with peptide and small-molecule agonists

Journal: Science Advances

Published: 2019-11-01

DOI: 10.1126/sciadv.aax9115

Affiliations: 17

Authors: 19

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Research Highlight

Better painkillers through structural biology

© JUAN GAERTNER/SCIENCE PHOTO LIBRARY/Getty

© JUAN GAERTNER/SCIENCE PHOTO LIBRARY/Getty

The atomic structures of a pain-relieving receptor in complex with activating drugs could help spur the development of safer painkillers.

Opioid painkillers are highly addictive and prone to abuse, leading to the so-called opioid epidemic in the USA. There is thus a need for safer, less addictive opioid painkillers that target a different receptor.

Using X-ray crystallography, a team co-led by scientists from ShanghaiTech University mapped the structure of the delta-opioid receptor in its active state while bound to one of two different agonist drugs, one a short protein and one a small molecule.

The researchers determined the structural basis for drug recognition, receptor activation and drug selectivity — and how those key factors differ between protein- and chemical-based drugs.

The findings should inform future structure-based design of opioid painkillers with more favourable pharmacological profiles and fewer side effects than existing options.

Supported content

  1. Science Advances 5, eaax9115 (2019). doi: 10.1126/sciadv.aax9115
Institutions Share
University of Southern California (USC), United States of America (USA) 0.31
Free University of Brussels (VUB), Belgium 0.16
ShanghaiTech University, China 0.15
University of Sherbrooke (USherbrooke), Canada 0.14
University of Bonn (Uni Bonn), Germany 0.09
Centre Hospitalier Universitaire de Sherbrooke (CHUS), Canada 0.07
GPCR Consortium, United States of America (USA) 0.05
CAS Center for Excellence in Molecular Cell Science, SIBS CAS, China 0.01
Institute of Biochemistry and Cell Biology (IBCB), SIBS CAS, China 0.01
University of Chinese Academy of Sciences (UCAS), Shanghai, China 0.01
University of Chinese Academy of Sciences (UCAS), China 0.01

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