Three-Dimensional Structural Insights Have Revealed the Distinct Binding Interactions of Agonists, Partial Agonists, and Antagonists with the µ Opioid Receptor

Li, Zoe; Liu, Jie; Dong, Fan; Chang, Nancy; Huang, Ruili; Xia, Menghang; Patterson, Tucker A.; Hong, Huixiao

doi:10.3390/ijms24087042

Three-Dimensional Structural Insights Have Revealed the Distinct Binding Interactions of Agonists, Partial Agonists, and Antagonists with the µ Opioid Receptor

Journal Article · Tue Apr 11 00:00:00 EDT 2023 · International Journal of Molecular Sciences (Online)

DOI:https://doi.org/10.3390/ijms24087042· OSTI ID:2425825

Li, Zoe ^[1]; Liu, Jie ^[1]; Dong, Fan ^[1]; Chang, Nancy ^[2]; Huang, Ruili ^[3]; Xia, Menghang ^[3]; Patterson, Tucker A. ^[1]; ^[1]

US Food and Drug Administration, Jefferson, AR (United States)
US Food and Drug Administration, Silver Spring, MD (United States)
National Institutes of Health, Bethesda, MD (United States)

The United States is experiencing the most profound and devastating opioid crisis in history, with the number of deaths involving opioids, including prescription and illegal opioids, continuing to climb over the past two decades. This severe public health issue is difficult to combat as opioids remain a crucial treatment for pain, and at the same time, they are also highly addictive. Opioids act on the opioid receptor, which in turn activates its downstream signaling pathway that eventually leads to an analgesic effect. Among the four types of opioid receptors, the µ subtype is primarily responsible for the analgesic cascade. This review describes available 3D structures of the µ opioid receptor in the protein data bank and provides structural insights for the binding of agonists and antagonists to the receptor. Comparative analysis on the atomic details of the binding site in these structures was conducted and distinct binding interactions for agonists, partial agonists, and antagonists were observed. The findings in this article deepen our understanding of the ligand binding activity and shed some light on the development of novel opioid analgesics which may improve the risk benefit balance of existing opioids.

View Accepted Manuscript (DOE)

Research Organization:: Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: SC0014664

OSTI ID:: 2425825

Journal Information:: International Journal of Molecular Sciences (Online), Journal Name: International Journal of Molecular Sciences (Online) Journal Issue: 8 Vol. 24; ISSN 1422-0067

Publisher:: MDPICopyright Statement

Country of Publication:: United States

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
Biochemistry & Molecular Biology
Chemistry
agonist
antagonist
binding
structure
µ opioid receptor

Three-Dimensional Structural Insights Have Revealed the Distinct Binding Interactions of Agonists, Partial Agonists, and Antagonists with the µ Opioid Receptor

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