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Structural and functional insights into σ 1 receptor ligand binding
Author(s) -
Schmidt Hayden Riley,
Kruse Andrew C
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.761.6
Subject(s) - receptor , functional selectivity , neuroscience , agonism , opioid receptor , g protein coupled receptor , ligand (biochemistry) , nop , 5 ht2a receptor , computational biology , psychology , pharmacology , biology , opioid , biochemistry , political science , 5 ht receptor , politics , serotonin , law
Originally misclassified as an opioid receptor, the σ 1 receptor is a single‐pass transmembrane protein with a diverse pharmacological profile. Though its precise biological function has proven elusive, the σ 1 receptor is thought to play a role in neurodegenerative diseases such as Parkinson's disease and ALS, as well as neurological pathologies, with the most notable being addiction and depression. A rich repertoire of ligands have emerged for the receptor, including both compounds traditionally associated with other targets, including haloperidol or cocaine, as well as (+) benzomorphans such as (+)‐pentazocine or unique ligands like PD 144418 or ditolylguanidine. Many of these compounds have been classified as agonists and antagonists, but the molecular distinction between the two classifications is not entirely clear. Here, we employ a combination of biochemical, pharmacological, and structural techniques to examine the basis for σ 1 receptor ligand binding and attempt to determine the molecular basis of agonism and antagonism for this enigmatic receptor. Support or Funding Information This work is supported by the National Science Foundation Graduate Research Fellowship awarded to HRS.