How μ-opioid receptor recognizes fentanyl.

Analgesics, Opioid / pharmacology Fentanyl / chemistry Ligands Models, Molecular Molecular Dynamics Simulation Morphine Receptors, Opioid, mu / chemistry Structure-Activity Relationship

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
12 02 2021
Historique:
received: 28 08 2020
accepted: 08 01 2021
entrez: 13 2 2021
pubmed: 14 2 2021
medline: 3 3 2021
Statut: epublish

Résumé

Roughly half of the drug overdose-related deaths in the United States are related to synthetic opioids represented by fentanyl which is a potent agonist of mu-opioid receptor (mOR). In recent years, X-ray crystal structures of mOR in complex with morphine derivatives have been determined; however, structural basis of mOR activation by fentanyl-like opioids remains lacking. Exploiting the X-ray structure of BU72-bound mOR and several molecular simulation techniques, we elucidated the detailed binding mechanism of fentanyl. Surprisingly, in addition to the salt-bridge binding mode common to morphinan opiates, fentanyl can move deeper and form a stable hydrogen bond with the conserved His297

Identifiants

DOI: 10.1038/s41467-021-21262-9 PMID: 33579956 PMC: PMC7881245
pubmed: 33579956
doi: 10.1038/s41467-021-21262-9
pii: 10.1038/s41467-021-21262-9
pmc: PMC7881245
doi:

Substances chimiques

Analgesics, Opioid 0
Ligands 0
Receptors, Opioid, mu 0
Morphine 76I7G6D29C
Fentanyl UF599785JZ

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

984

Subventions

Organisme : NIGMS NIH HHS
ID : R01 GM098818
Pays : United States

Commentaires et corrections

Type : UpdateOf
Type : UpdateOf

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Auteurs

Quynh N Vo (QN)

Center for Drug Evaluation and Research, United State Food and Drug Administration, Silver Spring, MD, USA.
Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD, USA.
ORCID: 0000-0003-3789-4880

Paween Mahinthichaichan (P)

Center for Drug Evaluation and Research, United State Food and Drug Administration, Silver Spring, MD, USA.
Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD, USA.

Jana Shen (J)

Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD, USA. jana.shen@rx.umaryland.edu.
ORCID: 0000-0002-3234-0769

Christopher R Ellis (CR)

Center for Drug Evaluation and Research, United State Food and Drug Administration, Silver Spring, MD, USA. christopher.ross.ellis@gmail.com.
ORCID: 0000-0002-3150-2981

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Classifications MeSH

questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Agents du système nerveux central › Dépresseurs du système nerveux central › Stupéfiants › Analgésiques morphiniques › How μ-opioid receptor recognizes fentanyl.
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Pipéridines › Fentanyl › How μ-opioid receptor recognizes fentanyl.
questionsmedicales.fr › Actions chimiques et utilisations › Utilisations spécialisées de produits chimiques › Produits chimiques de laboratoire › Ligands › How μ-opioid receptor recognizes fentanyl.
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles moléculaires › How μ-opioid receptor recognizes fentanyl.
questionsmedicales.fr › Sciences de l'information › Méthodologies informatiques › Simulation numérique › Simulation de dynamique moléculaire › How μ-opioid receptor recognizes fentanyl.
questionsmedicales.fr › Composés polycycliques › Hydrocarbures aromatiques polycycliques › Phénanthrènes › Morphinanes › Dérivés de la morphine › Morphine › How μ-opioid receptor recognizes fentanyl.
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs peptidiques › Récepteur aux neuropeptides › Récepteurs aux opioïdes › Récepteur mu › How μ-opioid receptor recognizes fentanyl.
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Relation structure-activité › How μ-opioid receptor recognizes fentanyl.