How μ-opioid receptor recognizes fentanyl.

ABSTRACT: 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 His297^6.52, which has been suggested to modulate mOR's ligand affinity and pH dependence by previo

SUBMITTER: Vo QN 

PROVIDER: S-EPMC7881245 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature