Structure of the human GluN1/GluN2A LBD in complex with compound 9 (GNE3500)

GluN2A-Selective Pyridopyrimidinone Series of NMDAR Positive Allosteric Modulators with an Improved in Vivo Profile.

liquid nitrogen-cooled dual crystal Si(111)

Ligand binding domain (UNP residues 401-539, GT linker, UNP residues 661-802)

UNP residues 394-544, GT linker, UNP residues 663-800

GluN2A, Glutamate [NMDA] receptor subunit epsilon-1, N-methyl D-aspartate receptor subtype 2A, hNR2A

GluN1, Glutamate [NMDA] receptor subunit zeta-1, N-methyl-D-aspartate receptor subunit NR1, NMD-R1

GSPDDNHLSIVTLEEAPFVIVEDIDPLTETCVRNTVPCRKFVKINNSTNEGMNVKKCCKGFCIDILKKLSRTVKFTYDLY
LVTNGKHGKKVNNVWNGMIGEVVYQRAVMAVGSLTINEERSEVVDFSVPFVETGISVMVSRGTQVTGLSDKKFQRPHDYS
PPFRFGTVPNGSTERNIRNNYPYMHQYMTKFNQKGVEDALVSLKTGKLDAFIYDAAVLNYKAGRDEGCKLVTIGSGYIFA
TTGYGIALQKGSPWKRQIDLALLQFVGDGEMEELETLWLTGICHN

GSMSTRLKIVTIHQEPFVYVKPTLSDGTCKEEFTVNGDPVKKVICTGPNDTSPGSPRHTVPQCCYGFCIDLLIKLARTMN
FTYEVHLVADGKFGTQERVNNSNKKEWNGMMGELLSGQADMIVAPLTINNERAQYIEFSKPFKYQGLTILVKKGTRITGI
NDPRLRNPSDKFIYATVKQSSVDIYFRRQVELSTMYRHMEKHNYESAAEAIQAVRDNKLHAFIWDSAVLEFEASQKCDLV
TTGELFFRSGFGIGMRKDSPWKQNVSLSILKSHENGFMEDLDKTWVRYQECDS

0.1 M HEPES, pH 7.0, 10-13% PEG8000, 2 mM calcium acetate

Glutamate receptor ionotropic, NMDA 2A, Glutamate receptor ionotropic, NMDA 1

NMDA receptor, glutamate, glycine, calcium channel, membrane, TRANSPORT PROTEIN

PDDNHLSIVTLEEAPFVIVEDIDPLTETCVRNTVPCRKFVKINNSTNEGMNVKKCCKGFCIDILKKLSRTVKFTYDLYLV
TNGKHGKKVNNVWNGMIGEVVYQRAVMAVGSLTINEERSEVVDFSVPFVETGISVMVSR

QVTGLSDKKFQRPHDYSPPFRFGTVPNGSTERNIRNNYPYMHQYMTKFNQKGVEDALVSLKTGKLDAFIYDAAVLNYKAG
RDEGCKLVTIGSGYIFATTGYGIALQKGSPWKRQIDLALLQFVGDGEMEELETLWLTGICHN

MSTRLKIVTIHQEPFVYVKPTLSDGTCKEEFTVNGDPVKKVICTGPNDTSPGSPRHTVPQCCYGFCIDLLIKLARTMNFT
YEVHLVADGKFGTQERVNNSNKKEWNGMMGELLSGQADMIVAPLTINNERAQYIEFSKPFKYQGLTILVKK

RITGINDPRLRNPSDKFIYATVKQSSVDIYFRRQVELSTMYRHMEKHNYESAAEAIQAVRDNKLHAFIWDSAVLEFEASQ
KCDLVTTGELFFRSGFGIGMRKDSPWKQNVSLSILKSHENGFMEDLDKTWVRYQECDS