MEDIA
Ligand binding to wild type and mutant GluN1 agonist binding domains
Representative molecular dynamics simulations from Rouzbeh et al., J Gen Physiol, 2023. In these simulations, the binding of glycine and the GluN1-selective competitive antagonists, CGP-78608 and L-689,560, is evaluated in the isolated agonist binding domain of the NMDA receptor subunit GluN1 with and without mutations in the binding site (FA+TL or FH+RK) that are known to abolish glycine binding.
1/23/2023
GluN1 ABD with glycine
Glycine is stably bound to wild type GluN1.
GluN1FA+TL ABD with glycine
Glycine readily unbinds from mutant GluN1FA+TL.
GluN1 ABD with CGP-78608
CGP-78608 is stably bound to wild type GluN1.
GluN1FA+TL ABD with CGP-78608
CGP-78608 unbinds from mutant GluN1FA+TL.
GluN1FH+RK ABD with CGP-78608
CGP-78608 remains partially bound to mutant GluN1FH+RK.
GluN1 ABD with L-689,560
L-689,560 is stably bound to wild type GluN1.
GluN1FA+TL ABD with L-689,560
L-689,560 is stably bound to mutant GluN1FA+TL.
GluN1FH+RK ABD with L-689,560
L-689,560 unbinds from mutant GluN1FH+RK.
Ligand binding to the glycine site in the GluN1 agonist binding domain
Representative molecular dynamics simulations from Rouzbeh et al., J Gen Physiol, 2023. These simulations suggest that binding of glycine and the GluN1-selective competitive antagonists, CGP-78608 and L-689,560, promotes distinct conformations of the GluN1 NMDA receptor agonist binding domain.
1/23/2023
GluN1 ABD with glycine
Molecular dynamics simulation (2500 ns) of glycine bound to the GluN1 NMDA receptor agonist binding domain.
GluN1 ABD with CGP-78608
Molecular dynamics simulation (2500 ns) of CGP-78608 bound to the GluN1 NMDA receptor agonist binding domain.
GluN1 ABD with L-689,560
Molecular dynamics simulation (2500 ns) of L-689,560 bound to the GluN1 NMDA receptor agonist binding domain.