Correlation Engine 2.0
Clear Search sequence regions


  • adopts (5)
  • alfentanil (1)
  • amine (20)
  • amino acids (1)
  • apo (19)
  • asp glu (3)
  • Asp2 (3)
  • Asp3 (1)
  • carfentanil (1)
  • case (1)
  • cholesterol (4)
  • CMAP (1)
  • crisis (1)
  • crystal (19)
  • damgo (7)
  • Dror (2)
  • ester (1)
  • factor (1)
  • fentanyl (133)
  • fluctuates (2)
  • GPCRs (7)
  • His6 (1)
  • hydrogen (8)
  • hydrogen bonds (26)
  • hydroxyl (1)
  • inform (1)
  • ligand (21)
  • light green (1)
  • lipid (6)
  • lipid x (1)
  • manner (1)
  • mass (5)
  • methyl (4)
  • morphinan (7)
  • mutagenesis (3)
  • near (2)
  • nitrogen (14)
  • norfentanyl (1)
  • opioids (8)
  • oxygen (1)
  • PDB (5)
  • peer review (1)
  • phenol (4)
  • POPC (2)
  • problem (1)
  • proteins membranes (1)
  • protocols (10)
  • proton (2)
  • receptor (9)
  • remifentanil (1)
  • research (1)
  • research design (1)
  • root (11)
  • salt (18)
  • shake (1)
  • sodium (4)
  • solvent (6)
  • sufentanil (1)
  • Waals (1)
  • β fna (7)
  • μ opioid receptor (2)
  • Sizes of these terms reflect their relevance to your search.

    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 His2976.52, which has been suggested to modulate mOR's ligand affinity and pH dependence by previous mutagenesis experiments. Intriguingly, this secondary binding mode is only accessible when His2976.52 adopts a neutral HID tautomer. Alternative binding modes may represent a general mechanism in G protein-coupled receptor-ligand recognition.

    Citation

    Quynh N Vo, Paween Mahinthichaichan, Jana Shen, Christopher R Ellis. How μ-opioid receptor recognizes fentanyl. Nature communications. 2021 Feb 12;12(1):984

    Expand section icon Mesh Tags

    Expand section icon Substances


    PMID: 33579956

    View Full Text