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Three-Dimensional Structural Insights Have Revealed the Distinct Binding Interactions of Agonists, Partial Agonists, and Antagonists with the µ Opioid Receptor
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 rema...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10138646/ https://www.ncbi.nlm.nih.gov/pubmed/37108204 http://dx.doi.org/10.3390/ijms24087042 |
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author | Li, Zoe Liu, Jie Dong, Fan Chang, Nancy Huang, Ruili Xia, Menghang Patterson, Tucker A. Hong, Huixiao |
author_facet | Li, Zoe Liu, Jie Dong, Fan Chang, Nancy Huang, Ruili Xia, Menghang Patterson, Tucker A. Hong, Huixiao |
author_sort | Li, Zoe |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10138646 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-101386462023-04-28 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 Int J Mol Sci Review 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. MDPI 2023-04-11 /pmc/articles/PMC10138646/ /pubmed/37108204 http://dx.doi.org/10.3390/ijms24087042 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Li, Zoe Liu, Jie Dong, Fan Chang, Nancy Huang, Ruili Xia, Menghang Patterson, Tucker A. Hong, Huixiao Three-Dimensional Structural Insights Have Revealed the Distinct Binding Interactions of Agonists, Partial Agonists, and Antagonists with the µ Opioid Receptor |
title | Three-Dimensional Structural Insights Have Revealed the Distinct Binding Interactions of Agonists, Partial Agonists, and Antagonists with the µ Opioid Receptor |
title_full | Three-Dimensional Structural Insights Have Revealed the Distinct Binding Interactions of Agonists, Partial Agonists, and Antagonists with the µ Opioid Receptor |
title_fullStr | Three-Dimensional Structural Insights Have Revealed the Distinct Binding Interactions of Agonists, Partial Agonists, and Antagonists with the µ Opioid Receptor |
title_full_unstemmed | Three-Dimensional Structural Insights Have Revealed the Distinct Binding Interactions of Agonists, Partial Agonists, and Antagonists with the µ Opioid Receptor |
title_short | Three-Dimensional Structural Insights Have Revealed the Distinct Binding Interactions of Agonists, Partial Agonists, and Antagonists with the µ Opioid Receptor |
title_sort | three-dimensional structural insights have revealed the distinct binding interactions of agonists, partial agonists, and antagonists with the µ opioid receptor |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10138646/ https://www.ncbi.nlm.nih.gov/pubmed/37108204 http://dx.doi.org/10.3390/ijms24087042 |
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