Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T62276 | Target Info | |||
| Target Name | Glutamate receptor ionotropic NMDA 1 (NMDAR1) | ||||
| Synonyms | NmethylDaspartate receptor subunit NR1; NMDR1; NMD-R1; N-methyl-D-aspartate receptor subunit NR1; Glutamate receptor ionotropic, NMDA 1; Glutamate [NMDA] receptor subunit zeta1; Glutamate [NMDA] receptor subunit zeta-1; GluN1 | ||||
| Target Type | Successful Target | ||||
| Gene Name | GRIN1 | ||||
| Biochemical Class | Glutamate-gated ion channel | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: Esketamine | Ligand Info | |||||
| Structure Description | Structure of the human GluN1-GluN2B NMDA receptor in complex with S-ketamine,glycine and glutamate | PDB:7EU8 | ||||
| Method | Electron microscopy | Resolution | 4.07 Å | Mutation | No | [1] |
| PDB Sequence |
NIGAVLSTRK
37 HEQMFREAVN47 QANKRIQLNA62 TSVTHKPNAI72 QMALSVCEDL82 ISSQVYAILV 92 SHPPTPNDHF102 TPTPVSYTAG112 FYRIPVLGLT122 TRMSIYSDKS132 IHLSFLRTVP 142 PYSHQSSVWF152 EMMRVYSWNH162 IILLVSDDHE172 GRAAQKRLET182 LLEESKAEKV 194 LQFDPGTKNV204 TALLMEAKEL214 EARVIILSAS224 EDDAATVYRA234 AAMLNMTGSG 244 YVWLVGEREI254 SGNALRYAPD264 GILGLQLING274 KNESAHISDA284 VGVVAQAVHE 294 LLEKENITDP304 PRGCVGNTNI314 WKTGPLFKRV324 LMSSKYADGV334 TGRVEFNEDG 344 DRKFANYSIM354 NLQNRKLVQV364 GIYNGTHVIP374 NDRKIIWPGG384 ETEKPRGYQM 394 STRLKIVTIH404 QEPFVYVKPT414 LSDGTCKEEF424 TVNGDPVKKV434 ICTGPNDTSP 444 GSPRHTVPQC454 CYGFCIDLLI464 KLARTMNFTY474 EVHLVADGKF484 GTQERKEWNG 500 MMGELLSGQA510 DMIVAPLTIN520 NERAQYIEFS530 KPFKYQGLTI540 LVKKEDSFMQ 556 PFQSTLWLLV566 GLSVHVVAVM576 LYLLDRLSSA606 MWFSWGVLLN616 SGSFSARILG 633 MVWAGFAMII643 VASYTANLAA653 FLVLDRPEER663 ITGINDPRLR673 NPSDKFIYAT 683 VKQSSVDIYF693 RRQVELSTMY703 RHMEKHNYES713 AAEAIQAVRD723 NKLHAFIWDS 733 AVLEFEASQK743 CDLVTTGELF753 FRSGFGIGMR763 KDSPWKQNVS773 LSILKSHENG 783 FMEDLDKTWV793 RYQECDTLTF810 ENMAGVFMLV820 AGGIVAGIFL830 IFIEIAYKRH 840 K
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| Ligand Name: [(1S)-1-{[(7-bromo-2,3-dioxo-1,2,3,4-tetrahydroquinoxalin-5-yl)methyl]amino}ethyl]phosphonic acid | Ligand Info | |||||
| Structure Description | Structure of the human GluN1/GluN2A NMDA receptor in the CGP-78608/glutamate bound state | PDB:7EOT | ||||
| Method | Electron microscopy | Resolution | 3.80 Å | Mutation | Yes | [2] |
| PDB Sequence |
KIVNIGAVLS
34 TRKHEQMFRE44 AVNQANKRHG54 SWKIQLNATS64 VTHKPNAIQM74 ALSVCEDLIS 84 SQVYAILVSH94 PPTPNDHFTP104 TPVSYTAGFY114 RIPVLGLTTR124 MSIYSDKSIH 134 LSFLRTVPPY144 SHQSSVWFEM154 MRVYSWNHII164 LLVSDDHEGR174 AAQKRLETLL 184 EERESKAEKV194 LQFDPGTKNV204 TALLMEAKEL214 EARVIILSAS224 EDDAATVYRA 234 AAMLNMTGSG244 YVWLVGEREI254 SGNALRYAPD264 GILGLQLING274 KNESAHISDA 284 VGVVAQAVHE294 LLEKENITDP304 PRGCVGNTNI314 WKTGPLFKRV324 LMSSKYADGV 334 TGRVEFNEDG344 DRKFANYSIM354 NLQNRKLVQV364 GIYNGTHVIP374 NDRKIIWPGG 384 ETEKPRGYQM394 STRLKIVTIH404 QEPFVYVKPT414 LSDGTCKEEF424 TVNGDPVKKV 434 ICTGPNDTSP444 GSPRHTVPQC454 CYGFCIDLLI464 KLARTMNFTY474 EVHLVADGKF 484 GTQERVNNSN494 KKEWNGMMGE504 LLSGQADMIV514 APLTINNERA524 QYIEFSKPFK 534 YQGLTILVKK544 EIPRSTLDSF554 MQPFQSTLWL564 LVGLSVHVVA574 VMLYLLDRFS 584 LTLSSAMWFS610 WGVLLNSGSF627 SARILGMVWA637 GFAMIIVASY647 TANLAAFLVL 657 DRPEERITGI667 NDPRLRNPSD677 KFIYATVKQS687 SVDIYFRRQV697 CLSTMYRHME 707 KHNYESAAEA717 IQAVRDNKLH727 AFIWDSAVLE737 FEASQKCDLV747 TTGELFFRSG 757 FGIGMRKDSP767 WKQNVSLSIL777 KSHENGFMED787 LDKTWVRYQE797 CTFENMAGVF 817 MLVAGGIVAG827 IFLIFIEIAY837 KRHKDAR
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| Ligand Name: 6-[[ethyl-(4-Fluorophenyl)amino]methyl]-2,3-Dihydro-1~{h}-Cyclopenta[3,4][1,3]thiazolo[1,4-~{a}]pyrimidin-8-One | Ligand Info | |||||
| Structure Description | Structure of the human GluN1/GluN2A LBD in complex with GNE8324 | PDB:5H8Q | ||||
| Method | X-ray diffraction | Resolution | 1.90 Å | Mutation | No | [3] |
| PDB Sequence |
TRLKIVTIHQ
14 EPFVYVKPTL24 SDGTCKEEFT34 VNGDPVKKVI44 CTGPNDTSPG54 SPRHTVPQCC 64 YGFCIDLLIK74 LARTMNFTYE84 VHLVADGKFG94 TQERVNKKEW107 NGMMGELLSG 117 QADMIVAPLT127 INNERAQYIE137 FSKPFKYQGL147 TILVKKGTRI157 TGINDPRLRN 167 PSDKFIYATV177 KQSSVDIYFR187 RQVELSTMYR197 HMEKHNYESA207 AEAIQAVRDN 217 KLHAFIWDSA227 VLEFEASQKC237 DLVTTGELFF247 RSGFGIGMRK257 DSPWKQNVSL 267 SILKSHENGF277 MEDLDKTWVR287 Y
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .5YE or .5YE2 or .5YE3 or :35YE;style chemicals stick;color identity;select .B:140 or .B:141 or .B:142 or .B:143 or .B:144 or .B:248 or .B:249 or .B:250 or .B:270 or .B:273; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 7-[(4-Fluoranylphenoxy)methyl]-3-[(1~{r},2~{r})-2-(Hydroxymethyl)cyclopropyl]-2-Methyl-[1,3]thiazolo[3,2-A]pyrimidin-5-One | Ligand Info | |||||
| Structure Description | Structure of the human GluN1/GluN2A LBD in complex with GNE6901 | PDB:5KCJ | ||||
| Method | X-ray diffraction | Resolution | 2.09 Å | Mutation | No | [3] |
| PDB Sequence |
TRLKIVTIHQ
14 EPFVYVKPTL24 SDGTCKEEFT34 VNGDPVKKVI44 CTGPNDTSPG54 SPRHTVPQCC 64 YGFCIDLLIK74 LARTMNFTYE84 VHLVADGKFG94 TQERVNKKEW107 NGMMGELLSG 117 QADMIVAPLT127 INNERAQYIE137 FSKPFKYQGL147 TILVKKGTRI157 TGINDPRLRN 167 PSDKFIYATV177 KQSSVDIYFR187 RQVELSTMYR197 HMEKHNYESA207 AEAIQAVRDN 217 KLHAFIWDSA227 VLEFEASQKC237 DLVTTGELFF247 RSGFGIGMRK257 DSPWKQNVSL 267 SILKSHENGF277 MEDLDKTWVR287
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .6RM or .6RM2 or .6RM3 or :36RM;style chemicals stick;color identity;select .B:128 or .B:140 or .B:141 or .B:144 or .B:249 or .B:250 or .B:270 or .B:273; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: N-Ethyl-7-{[2-Fluoro-3-(Trifluoromethyl)phenyl]methyl}-2-Methyl-5-Oxo-5h-[1,3]thiazolo[3,2-A]pyrimidine-3-Carboxamide | Ligand Info | |||||
| Structure Description | Structure of the human GluN1/GluN2A LBD in complex with N-ethyl-7-{[2-fluoro-3-(trifluoromethyl)phenyl]methyl}-2-methyl-5-oxo-5H-[1,3]thiazolo[3,2-a]pyrimidine-3-carboxamide (compound 29) | PDB:5I2N | ||||
| Method | X-ray diffraction | Resolution | 2.12 Å | Mutation | No | [4] |
| PDB Sequence |
MSTRLKIVTI
12 HQEPFVYVKP22 TLSDGTCKEE32 FTVNGDPVKK42 VICTGPNDTS52 PGSPRHTVPQ 62 CCYGFCIDLL72 IKLARTMNFT82 YEVHLVADGK92 FGTQERVNKK105 EWNGMMGELL 115 SGQADMIVAP125 LTINNERAQY135 IEFSKPFKYQ145 GLTILVKKGT155 RITGINDPRL 165 RNPSDKFIYA175 TVKQSSVDIY185 FRRQVELSTM195 YRHMEKHNYE205 SAAEAIQAVR 215 DNKLHAFIWD225 SAVLEFEASQ235 KCDLVTTGEL245 FFRSGFGIGM255 RKDSPWKQNV 265 SLSILKSHEN275 GFMEDLDKTW285 VR
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .67J or .67J2 or .67J3 or :367J;style chemicals stick;color identity;select .B:140 or .B:141 or .B:142 or .B:143 or .B:144 or .B:248 or .B:249 or .B:250 or .B:269 or .B:270 or .B:273; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 7-[[ethyl(Phenyl)amino]methyl]-2-Methyl-[1,3,4]thiadiazolo[3,2-A]pyrimidin-5-One | Ligand Info | |||||
| Structure Description | Structure of the human GluN1/GluN2A LBD in complex with GNE3419 | PDB:5H8H | ||||
| Method | X-ray diffraction | Resolution | 2.23 Å | Mutation | No | [3] |
| PDB Sequence |
MSTRLKIVTI
12 HQEPFVYVKP22 TLSDGTCKEE32 FTVNGDPVKK42 VICTGPNDTS52 PGSPRHTVPQ 62 CCYGFCIDLL72 IKLARTMNFT82 YEVHLVADGK92 FGTQERVNKK105 EWNGMMGELL 115 SGQADMIVAP125 LTINNERAQY135 IEFSKPFKYQ145 GLTILVKKGT155 RITGINDPRL 165 RNPSDKFIYA175 TVKQSSVDIY185 FRRQVELSTM195 YRHMEKHNYE205 SAAEAIQAVR 215 DNKLHAFIWD225 SAVLEFEASQ235 KCDLVTTGEL245 FFRSGFGIGM255 RKDSPWKQNV 265 SLSILKSHEN275 GFMEDLDKTW285 VR
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .5YC or .5YC2 or .5YC3 or :35YC;style chemicals stick;color identity;select .B:140 or .B:141 or .B:142 or .B:143 or .B:144 or .B:249 or .B:250 or .B:270 or .B:273; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 7-[[5-chloro-3-(trifluoromethyl)-1H-pyrazol-1-yl]methyl]-N-ethyl-2-methyl-5-oxo-5H-[1,3]thiazolo[3,2-a]pyrimidine-3-carboxamide | Ligand Info | |||||
| Structure Description | Structure of the human GluN1/GluN2A LBD in complex with compound 2 (GNE9178) | PDB:5TP9 | ||||
| Method | X-ray diffraction | Resolution | 2.40 Å | Mutation | No | [5] |
| PDB Sequence |
MSTRLKIVTI
12 HQEPFVYVKP22 TLSDGTCKEE32 FTVNGDPVKK42 VICTGPNDTS52 PGSPRHTVPQ 62 CCYGFCIDLL72 IKLARTMNFT82 YEVHLVADGK92 FGTQERVNKK105 EWNGMMGELL 115 SGQADMIVAP125 LTINNERAQY135 IEFSKPFKYQ145 GLTILVKKGT155 RITGINDPRL 165 RNPSDKFIYA175 TVKQSSVDIY185 FRRQVELSTM195 YRHMEKHNYE205 SAAEAIQAVR 215 DNKLHAFIWD225 SAVLEFEASQ235 KCDLVTTGEL245 FFRSGFGIGM255 RKDSPWKQNV 265 SLSILKSHEN275 GFMEDLDKTW285 VRYQ
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .7H0 or .7H02 or .7H03 or :37H0;style chemicals stick;color identity;select .B:140 or .B:141 or .B:142 or .B:143 or .B:144 or .B:248 or .B:249 or .B:250 or .B:269 or .B:270 or .B:273; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: CID 127046129 | Ligand Info | |||||
| Structure Description | Structure of the human GluN1/GluN2A LBD in complex with GNE0723 | PDB:5KDT | ||||
| Method | X-ray diffraction | Resolution | 2.44 Å | Mutation | No | [4] |
| PDB Sequence |
MSTRLKIVTI
12 HQEPFVYVKP22 TLSDGTCKEE32 FTVNGDPVKK42 VICTGPNDTS52 PGSPRHTVPQ 62 CCYGFCIDLL72 IKLARTMNFT82 YEVHLVADGK92 FGTQERVNKK105 EWNGMMGELL 115 SGQADMIVAP125 LTINNERAQY135 IEFSKPFKYQ145 GLTILVKKGT155 RITGINDPRL 165 RNPSDKFIYA175 TVKQSSVDIY185 FRRQVELSTM195 YRHMEKHNYE205 SAAEAIQAVR 215 DNKLHAFIWD225 SAVLEFEASQ235 KCDLVTTGEL245 FFRSGFGIGM255 RKDSPWKQNV 265 SLSILKSHEN275 GFMEDLDKTW285 VRYQ
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .6RV or .6RV2 or .6RV3 or :36RV;style chemicals stick;color identity;select .B:128 or .B:140 or .B:141 or .B:142 or .B:143 or .B:144 or .B:248 or .B:249 or .B:250 or .B:270 or .B:273; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: (1r,2r)-2-(2-{[5-Chloro-3-(Trifluoromethyl)-1h-Pyrazol-1-Yl]methyl}-7-Methyl-4-Oxo-4h-Pyrido[1,2-A]pyrimidin-6-Yl)cyclopropane-1-Carbonitrile | Ligand Info | |||||
| Structure Description | Structure of the human GluN1/GluN2A LBD in complex with compound 9 (GNE3500) | PDB:5TPA | ||||
| Method | X-ray diffraction | Resolution | 2.48 Å | Mutation | No | [5] |
| PDB Sequence |
MSTRLKIVTI
12 HQEPFVYVKP22 TLSDGTCKEE32 FTDPVKKVIC45 TGPNDTSPGS55 PRHTVPQCCY 65 GFCIDLLIKL75 ARTMNFTYEV85 HLVADGKFGT95 QERVKKEWNG109 MMGELLSGQA 119 DMIVAPLTIN129 NERAQYIEFS139 KPFKYQGLTI149 LVKKGTRITG159 INDPRLRNPS 169 DKFIYATVKQ179 SSVDIYFRRQ189 VELSTMYRHM199 EKHNYESAAE209 AIQAVRDNKL 219 HAFIWDSAVL229 EFEASQKCDL239 VTTGELFFRS249 GFGIGMRKDS259 PWKQNVSLSI 269 LKSHENGFME279 DLDKTWVRC
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .7H2 or .7H22 or .7H23 or :37H2;style chemicals stick;color identity;select .B:128 or .B:140 or .B:141 or .B:142 or .B:143 or .B:144 or .B:248 or .B:249 or .B:250 or .B:269 or .B:270 or .B:273; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 4-[[(4-Fluorophenyl)sulfonylamino]methyl]-~{n}-(Pyridin-3-Ylmethyl)benzamide | Ligand Info | |||||
| Structure Description | Structure of the human GluN1/GluN2A LBD in complex with NAM | PDB:5H8N | ||||
| Method | X-ray diffraction | Resolution | 2.50 Å | Mutation | No | [3] |
| PDB Sequence |
TRLKIVTIHQ
14 EPFVYVKPTL24 SDGTCKEEFT34 VNGDPVKKVI44 CTGPNDTSPG54 SPRHTVPQCC 64 YGFCIDLLIK74 LARTMNFTYE84 VHLVADGKFG94 TQERVNKKEW107 NGMMGELLSG 117 QADMIVAPLT127 INNERAQYIE137 FSKPFKYQGL147 TILVKKGTRI157 TGINDPRLRN 167 PSDKFIYATV177 KQSSVDIYFR187 RQVELSTMYR197 HMEKHNYESA207 AEAIQAVRDN 217 KLHAFIWDSA227 VLEFEASQKC237 DLVTTGELFF247 RSGFGIGMRK257 DSPWKQNVSL 267 SILKSHENGF277 MEDLDKTWVR287 YQ
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .5YD or .5YD2 or .5YD3 or :35YD;style chemicals stick;color identity;select .B:128 or .B:141 or .B:144 or .B:145 or .B:248 or .B:249 or .B:250 or .B:251; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 7-{[ethyl(4-Fluorophenyl)amino]methyl}-N,2-Dimethyl-5-Oxo-5h-[1,3]thiazolo[3,2-A]pyrimidine-3-Carboxamide | Ligand Info | |||||
| Structure Description | Structure of the human GluN1/GluN2A LBD in complex with 7-{[ethyl(4-fluorophenyl)amino]methyl}-N,2-dimethyl-5-oxo-5H-[1,3]thiazolo[3,2-a]pyrimidine-3-carboxamide (compound 19) | PDB:5I2K | ||||
| Method | X-ray diffraction | Resolution | 2.86 Å | Mutation | No | [4] |
| PDB Sequence |
MSTRLKIVTI
12 HQEPFVYVKP22 TLSDGTCKEE32 FTVNGDPVKK42 VICTGPNDTS52 PGSPRHTVPQ 62 CCYGFCIDLL72 IKLARTMNFT82 YEVHLVADGK92 FGTQERVNKK105 EWNGMMGELL 115 SGQADMIVAP125 LTINNERAQY135 IEFSKPFKYQ145 GLTILVKKGT155 RITGINDPRL 165 RNPSDKFIYA175 TVKQSSVDIY185 FRRQVELSTM195 YRHMEKHNYE205 SAAEAIQAVR 215 DNKLHAFIWD225 SAVLEFEASQ235 KCDLVTTGEL245 FFRSGFGIGM255 RKDSPWKQNV 265 SLSILKSHEN275 GFMEDLDKTW285 VRYQEC
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .67H or .67H2 or .67H3 or :367H;style chemicals stick;color identity;select .B:128 or .B:140 or .B:141 or .B:142 or .B:143 or .B:144 or .B:248 or .B:249 or .B:250 or .B:270 or .B:273; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Structural basis of ketamine action on human NMDA receptors. Nature. 2021 Aug;596(7871):301-305. | ||||
| REF 2 | Gating mechanism and a modulatory niche of human GluN1-GluN2A NMDA receptors. Neuron. 2021 Aug 4;109(15):2443-2456.e5. | ||||
| REF 3 | Positive Allosteric Modulators of GluN2A-Containing NMDARs with Distinct Modes of Action and Impacts on Circuit Function. Neuron. 2016 Mar 2;89(5):983-99. | ||||
| REF 4 | Discovery of GluN2A-Selective NMDA Receptor Positive Allosteric Modulators (PAMs): Tuning Deactivation Kinetics via Structure-Based Design. J Med Chem. 2016 Mar 24;59(6):2760-79. | ||||
| REF 5 | GluN2A-Selective Pyridopyrimidinone Series of NMDAR Positive Allosteric Modulators with an Improved in Vivo Profile. ACS Med Chem Lett. 2016 Oct 31;8(1):84-89. | ||||
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