TABLE 2

Experimentally obtained structures of prokaryotic LGIC with pharmacologic and physiologically relevant compounds

All modulators described here were cocrystallized with their respective receptors allowing the analysis and description of each binding site.

ReceptorModulatorPDB CodeMolecular or Pharmacologic EffectsGlyRaReference
GLICDesflurane3P4WInhibition (IC50 = 27 ± 13 μM)+Nury et al., 2011
Propofol3P50Inhibition (IC50 = 24 ± 6.3 μM)+Nury et -al., 2011
Ketamine4F8HInhibition (IC50 = 58 μM)+Pan et al., 2012a
Bromoform4HFHInhibition in GLIC wild type+Sauguet et al., 2013a
4HFDPotentiation by 1 mM (F14ʹA ethanol-sensitive mutant)Sauguet et al., 2013a
5HCMLocally closed conformationLaurent et al., 2016
(2–21ʹ cross-linked mutant)
Zinc2XQ8Inhibition by pore blocker+/−Hilf et al., 2010
Xenon4ZZBInhibition (IC50 = 1.05 atm)+Weng et al., 2010; Sauguet et al., 2016
4ZZC
Cesium2XQ6Inhibition by pore blockerWEHilf et al., 2010
4ILAInhibition by pore blocker (GLIC A237F mutant)Sauguet et al., 2013b
Ethanol4HFEPotentiation by low ethanol ≥20 μM (F14ʹA ethanol-sensitive mutant)+Sauguet et al., 2013a
GLIC wild type insensitive to ethanol
ELICIsoflurane4Z90Resting state, in absence of agonists+Chen et al., 2015
4Z91Desensitized state – in presence of agonists Inhibition on ELIC (IC50 = 21.9 ± 1.5 μM)Chen et al., 2015
Bromo-flurazepam4A98Potentiation similar to flurazepam+Spurny et al., 2012
GABA and flurazepam2YOEPotentiation flurazepam ≤50 μM and inhibition at higher concentrations (biphasic effects)+Spurny et al., 2012
Zopiclone4A97Inhibition ∼90% by 10 μMNASpurny et al., 2012
Bromoform3ZKRInhibition (IC50 = 125 ± 10 μM)+Spurny et al., 2013
Barium2YN6Inhibition by decreasing agonist efficacy and blocking channel openingWEZimmermann et al., 2012
Memantine4TWDInhibition by pore-blocking and affecting agonist binding site (IC50 = 118 μM)WEUlens et al., 2014
Bromo-memantine4TWFInhibition similar to memantineWEUlens et al., 2014
  • + , Potentiation, +/−, biphasic effect; NA, not available; WE, without effect.

  • a Refers to the most reported effect.