{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T12:54:20Z","timestamp":1782996860769,"version":"3.54.5"},"reference-count":68,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T00:00:00Z","timestamp":1717372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The opioid crisis in the United States is a significant public health issue, with a nearly threefold increase in opioid-related fatalities between 1999 and 2014. In response to this crisis, society has made numerous efforts to mitigate its impact. Recent advancements in understanding the structural intricacies of the \u03ba opioid receptor (KOR) have improved our knowledge of how opioids interact with their receptors, triggering downstream signaling pathways that lead to pain relief. This review concentrates on the KOR, offering crucial structural insights into the binding mechanisms of both agonists and antagonists to the receptor. Through comparative analysis of the atomic details of the binding site, distinct interactions specific to agonists and antagonists have been identified. These insights not only enhance our understanding of ligand binding mechanisms but also shed light on potential pathways for developing new opioid analgesics with an improved risk-benefit profile.<\/jats:p>","DOI":"10.3390\/molecules29112635","type":"journal-article","created":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T12:19:46Z","timestamp":1717417186000},"page":"2635","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Decoding the \u03ba Opioid Receptor (KOR): Advancements in Structural Understanding and Implications for Opioid Analgesic Development"],"prefix":"10.3390","volume":"29","author":[{"given":"Zoe","family":"Li","sequence":"first","affiliation":[{"name":"National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR 72079, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruili","family":"Huang","sequence":"additional","affiliation":[{"name":"National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menghang","family":"Xia","sequence":"additional","affiliation":[{"name":"National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Chang","sequence":"additional","affiliation":[{"name":"Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD 20993, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Guo","sequence":"additional","affiliation":[{"name":"National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR 72079, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Liu","sequence":"additional","affiliation":[{"name":"National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR 72079, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Dong","sequence":"additional","affiliation":[{"name":"National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR 72079, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bailang","family":"Liu","sequence":"additional","affiliation":[{"name":"National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR 72079, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Varghese","sequence":"additional","affiliation":[{"name":"National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR 72079, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aasma","family":"Aslam","sequence":"additional","affiliation":[{"name":"National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR 72079, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tucker A.","family":"Patterson","sequence":"additional","affiliation":[{"name":"National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR 72079, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8087-3968","authenticated-orcid":false,"given":"Huixiao","family":"Hong","sequence":"additional","affiliation":[{"name":"National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.15585\/mmwr.mm655051e1","article-title":"Increases in Drug and Opioid-Involved Overdose Deaths\u2014United States, 2010\u20132015","volume":"65","author":"Rudd","year":"2016","journal-title":"MMWR Morb. 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