Several gas binding sites in the ligand binding domains of the N-methyl D-aspartate receptor
Abstract
Using nitrous oxide as a probe, gas binding sites were looked for in the ligand binding domains of the three main subunits of the NMDA receptor, their affinity for nitrous oxide being assessed using state-of-the-art free energy calculations. For six of them, nitrous oxide is found to have an affinity that is better than for the well-studied gas binding sites of urate oxidase.
Interestingly, two of these sites were previously found in the ligand binding domain of the GluN1 subunit, when xenon was used as a probe. However, the best binding sites for nitrous oxide are found in the GluN2B subunit, in a pair of large hydrophobic pockets. Intriguingly, the sidechain of Cys461, whose mutation is associated to intellectual disability and epilepsy, protrudes into one of them, which is next to the binding site of the glutamate agonist, suggesting that this pocket may play a role in the normal function of the NMDA receptor.
Since nitrous oxide similarly affects GluN2A and GluN2B containing NMDA receptors, it is likely that nitrous oxide can also bind to domains other than the ligand binding ones, for instance near the cation pore where other dissociative anesthetics, like ketamine or memantine, are known to bind.
Related
- Evolution of NELL binding by dual-ligand-responsive axon guidance receptor Robo
- On the interpretation of the kinetics of ligand-receptor binding
- Ligand-binding/transcriptional repressor domain-deficient REV-ERBβ inhibits dendrite and spine formation of newborn adult hippocampal neurons
- ToxINsight: An Integrated Web Platform for Sequence, Structure, and Ligand Binding Analysis of Snake Venom Toxins
- From neuropeptide and receptor annotation to ligand-receptor pairing: a sequence- and structure-based framework for mapping the neuropeptide-receptor interactome in Gryllus bimaculatus
BibTeX
@misc{allouche2026several,
title = {{Several gas binding sites in the ligand binding domains of the N-methyl D-aspartate receptor}},
author = {David Allouche and Yves-Henri Sanejouand},
howpublished = {HAL},
year = {2026},
month = nov,
url = {https://hal.science/hal-05858221v1},
note = {CC BY-ND 4.0},
}
RIS
TY - UNPB
TI - Several gas binding sites in the ligand binding domains of the N-methyl D-aspartate receptor
AU - David Allouche
AU - Yves-Henri Sanejouand
PY - 2026
DA - 2026/11/02
PB - HAL
UR - https://hal.science/hal-05858221v1
AB - Using nitrous oxide as a probe, gas binding sites were looked for in the ligand binding domains of the three main subunits of the NMDA receptor, their affinity for nitrous oxide being assessed using state-of-the-art free energy calculations. For six of them, nitrous oxide is found to have an affinity that is better than for the well-studied gas binding sites of urate oxidase. Interestingly, two of these sites were previously found in the ligand binding domain of the GluN1 subunit, when xenon was used as a probe. However, the best binding sites for nitrous oxide are found in the GluN2B subunit, in a pair of large hydrophobic pockets. Intriguingly, the sidechain of Cys461, whose mutation is associated to intellectual disability and epilepsy, protrudes into one of them, which is next to the binding site of the glutamate agonist, suggesting that this pocket may play a role in the normal function of the NMDA receptor. Since nitrous oxide similarly affects GluN2A and GluN2B containing NMDA receptors, it is likely that nitrous oxide can also bind to domains other than the ligand binding ones, for instance near the cation pore where other dissociative anesthetics, like ketamine or memantine, are known to bind.
ER -