Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T22285 | Target Info | |||
| Target Name | Glutamate receptor ionotropic NMDA 2A (NMDAR2A) | ||||
| Synonyms | NR2A; NMDA receptor NR2A; N-methyl D-aspartate receptor subtype 2A; HNR2A; Glutamate receptor ionotropic, NMDA 2A; Glutamate [NMDA] receptor subunit epsilon-1; GluN2A | ||||
| Target Type | Successful Target | ||||
| Gene Name | GRIN2A | ||||
| Biochemical Class | Glutamate-gated ion channel | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: (2R)-4-(3-phosphonopropyl)piperazine-2-carboxylic acid | Ligand Info | |||||
| Structure Description | Structure of the human GluN1/GluN2A NMDA receptor in the glycine/CPP bound state | PDB:7EOQ | ||||
| Method | Electron microscopy | Resolution | 4.10 Å | Mutation | Yes | [1] |
| PDB Sequence |
LNIAVMLGHS
43 HDVTERELRT53 LWGPEQAAGL63 PLDVNVVALL73 MNRTDPKSLI83 THVCDLMSGA 93 RIHGLVFGDD103 TDQEAVAQML113 DFISSHTFVP123 ILGIHGGASM133 IMADKDPTST 143 FFQFGASIQQ153 QATVMLKIMQ163 DYDWHVFSLV173 TTIFPGYREF183 ISFVKTTVDN 193 SFVGWDMQNV203 ITLDTSFEDA213 KTQVQLKKIH223 SSVILLYCSK233 DEAVLILSEA 243 RSLGLTGYDF253 FWIVPSLVSG263 NTELIPKEFP273 SGLISVSYDD283 WDYSLEARVR 293 DGIGILTTAA303 SSMLEKFSYI313 PEAKASCYGQ323 MERPEVPMHT333 LHPFMVNVTW 343 DGKDLSFTEE353 GYQVHPRLVV363 IVLNKDREWE373 KVGKWENHTL383 SLRHAVWPRY 393 KSFSDCEPDD403 NHLSIVTLEE413 APFVIVEDID423 PLTETCVRNT433 VPCRKFVKIN 443 NSTNEGMNVK453 KCCKGFCIDI463 LKKLSRTVKF473 TYDLYLVTNG483 KHGKKVNNVW 493 NGMIGEVVYQ503 RAVMAVGSLT513 INEERSEVVD523 FSVPFVETGI533 SVMVSRSNGT 543 VSPSAFLEPF553 SASVWVMMFV563 MLLIVSAIAV573 FVFEYFSPSF599 TIGKAIWLLW 609 GLVFNNSVPV619 QNPKGTTSKI629 MVSVWAFFAV639 IFLASYTANL649 AAFMIQFVDQ 661 VTGLSDKKFQ671 RPHDYSPPFR681 FGTVPNGSTE691 RNIRNNYPYM701 HQYMTKFNQK 711 GVEDALVSLK721 TGKLDAFIYD731 AAVLNYKAGR741 DEGCKLVTIG751 SGYIFATTGY 761 GIALQKGSPW771 KRQIDLALLQ781 FVGDGEMEEL791 ETCWLTGICH801 NEVMSSQLDI 814 DNMAGVFYML824 AAAMALSLIT834 FIW
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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 | [2] |
| PDB Sequence |
NHLSIVTLEE
15 APFVIVEDID25 PETCVRNTVP37 CRKFVKINNS47 TNEGMNVKKC57 CKGFCIDILK 67 KLSRTVKFTY77 DLYLVTNGKH87 GKKVNNVWNG97 MIGEVVYQRA107 VMAVGSLTIN 117 EERSEVVDFS127 VPFVETGISV137 MVSRGTQVTG147 LSDKKFQRPH157 DYSPPFRFGT 167 VPNGSTERNI177 RNNYPYMHQY187 MTKFNQKGVE197 DALVSLKTGK207 LDAFIYDAAV 217 LNYKAGRDEG227 CKLVTIGSGY237 IFATTGYGIA247 LQKGSPWKRQ257 IDLALLQFVG 267 DGEMEELETL277 WLTGIC
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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 | [2] |
| PDB Sequence |
DNHLSIVTLE
14 EAPFVIVEDI24 DPLTETCVRN34 TVPCRKFVKI44 NNSTNEGMNV54 KKCCKGFCID 64 ILKKLSRTVK74 FTYDLYLVTN84 GKHGKKVNNV94 WNGMIGEVVY104 QRAVMAVGSL 114 TINEERSEVV124 DFSVPFVETG134 ISVMVSRGTQ144 VTGLSDKKFQ154 RPHDYSPPFR 164 FGTVPNGSTE174 RNIRNNYPYM184 HQYMTKFNQK194 GVEDALVSLK204 TGKLDAFIYD 214 AAVLNYKAGR224 DEGCKLVTIG234 SGYIFATTGY244 GIALQKGSPW254 KRQIDLALLQ 264 FVGDGEMEEL274 ETLWLTGIC
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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 .A:116 or .A:128 or .A:129 or .A:130 or .A:131 or .A:132 or .A:241 or .A:242 or .A:243 or .A:263 or .A:266; color #00ffc7; 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 | [3] |
| PDB Sequence |
DNHLSIVTLE
14 EAPFVIVEDI24 DPETCVRNTV36 PCRKFVKINN46 STNEGMNVKK56 CCKGFCIDIL 66 KKLSRTVKFT76 YDLYLVTNGK86 HGKKVNNVWN96 GMIGEVVYQR106 AVMAVGSLTI 116 NEERSEVVDF126 SVPFVETGIS136 VMVSRGTQVT146 GLSDKKFQRP156 HDYSPPFRFG 166 TVPNGSTERN176 IRNNYPYMHQ186 YMTKFNQKGV196 EDALVSLKTG206 KLDAFIYDAA 216 VLNYKAGRDE226 GCKLVTIGSG236 YIFATTGYGI246 ALQKGSPWKR256 QIDLALLQFV 266 GDGEMEELET276 LWLTGIC
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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 .A:116 or .A:128 or .A:129 or .A:130 or .A:131 or .A:132 or .A:133 or .A:241 or .A:242 or .A:243 or .A:262 or .A:263 or .A:266 or .A:271 or .A:275; 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(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 | [2] |
| PDB Sequence |
DNHLSIVTLE
14 EAPFVIVEDI24 DPETCVRNTV36 PCRKFVKINN46 STNEGMNVKK56 CCKGFCIDIL 66 KKLSRTVKFT76 YDLYLVTNGK86 HGKKVNNVWN96 GMIGEVVYQR106 AVMAVGSLTI 116 NEERSEVVDF126 SVPFVETGIS136 VMVSRGTQVT146 GLSDKKFQRP156 HDYSPPFRFG 166 TVPNGSTERN176 IRNNYPYMHQ186 YMTKFNQKGV196 EDALVSLKTG206 KLDAFIYDAA 216 VLNYKAGRDE226 GCKLVTIGSG236 YIFATTGYGI246 ALQKGSPWKR256 QIDLALLQFV 266 GDGEMEELET276 LWLTGIC
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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 .A:116 or .A:129 or .A:130 or .A:131 or .A:132 or .A:241 or .A:242 or .A:243 or .A:266; 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-[[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 | [4] |
| PDB Sequence |
NHLSIVTLEE
15 APFVIVEDID25 ETCVRNTVPC38 RKFVKINNST48 NEGMNVKKCC58 KGFCIDILKK 68 LSRTVKFTYD78 LYLVTNGKHG88 KKVNNVWNGM98 IGEVVYQRAV108 MAVGSLTINE 118 ERSEVVDFSV128 PFVETGISVM138 VSRGTQVTGL148 SDKKFQRPHD158 YSPPFRFGTV 168 PNGSTERNIR178 NNYPYMHQYM188 TKFNQKGVED198 ALVSLKTGKL208 DAFIYDAAVL 218 NYKAGRDEGC228 KLVTIGSGYI238 FATTGYGIAL248 QKGSPWKRQI258 DLALLQFVGD 268 GEMEELETLW278 LTGIC
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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 .A:116 or .A:128 or .A:129 or .A:130 or .A:131 or .A:132 or .A:241 or .A:242 or .A:243 or .A:262 or .A:263 or .A:266 or .A:271 or .A:275; color #f3c393; 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 | [3] |
| PDB Sequence |
DNHLSIVTLE
14 EAPFVIVEDI24 DPETCVRNTV36 PCRKFVKINN46 STNEGMNVKK56 CCKGFCIDIL 66 KKLSRTVKFT76 YDLYLVTNGK86 HGKKVNNVWN96 GMIGEVVYQR106 AVMAVGSLTI 116 NEERSEVVDF126 SVPFVETGIS136 VMVSRGTQVT146 GLSDKKFQRP156 HDYSPPFRFG 166 TVPNGSTERN176 IRNNYPYMHQ186 YMTKFNQKGV196 EDALVSLKTG206 KLDAFIYDAA 216 VLNYKAGRDE226 GCKLVTIGSG236 YIFATTGYGI246 ALQKGSPWKR256 QIDLALLQFV 266 GDGEMEELET276 LWLTGICH
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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 .A:116 or .A:128 or .A:129 or .A:130 or .A:131 or .A:132 or .A:241 or .A:242 or .A:243 or .A:263 or .A:266 or .A:271 or .A:275; color #00ffc7; 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 | [4] |
| PDB Sequence |
NHLSIVTLEE
15 APFVIVEDID25 ETCVRNTVPC38 RKFVKINNST48 NEGMNVKKCC58 KGFCIDILKK 68 LSRTVKFTYD78 LYLVTNGKHG88 KKVNNVWNGM98 IGEVVYQRAV108 MAVGSLTINE 118 ERSEVVDFSV128 PFVETGISVM138 VSRGTQVTGL148 SDKKFQRPHD158 YSPPFRFGTV 168 PNGSTERNIR178 NNYPYMHQYM188 TKFNQKGVED198 ALVSLKTGKL208 DAFIYDAAVL 218 NYKAGRDEGC228 KLVTIGSGYI238 FATTGYGIAL248 QKGSPWKRQI258 DLALLQFVGD 268 GEMEELETLW278 LTGIC
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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 .A:116 or .A:128 or .A:129 or .A:130 or .A:131 or .A:132 or .A:241 or .A:242 or .A:243 or .A:263 or .A:266 or .A:271; color #f3c393; 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 | [2] |
| PDB Sequence |
NHLSIVTLEE
15 APFVIVEDID25 PETCVRNTVP37 CRKFVKINNS47 TNEGMNVKKC57 CKGFCIDILK 67 KLSRTVKFTY77 DLYLVTNGKH87 GKKVNNVWNG97 MIGEVVYQRA107 VMAVGSLTIN 117 EERSEVVDFS127 VPFVETGISV137 MVSRGTQVTG147 LSDKKFQRPH157 DYSPPFRFGT 167 VPNGSTERNI177 RNNYPYMHQY187 MTKFNQKGVE197 DALVSLKTGK207 LDAFIYDAAV 217 LNYKAGRDEG227 CKLVTIGSGY237 IFATTGYGIA247 LQKGSPWKRQ257 IDLALLQFVG 267 DGEMEELETL277 WLTGIC
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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 .A:61 or .A:128 or .A:129 or .A:130 or .A:131 or .A:132 or .A:263 or .A:266 or .A:271 or .A:275 or .A:279; 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(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 | [3] |
| PDB Sequence |
NHLSIVTLEE
15 APFVIVEDID25 PETCVRNTVP37 CRKFVKINNS47 TNEGMNVKKC57 CKGFCIDILK 67 KLSRTVKFTY77 DLYLVTNGKH87 GKKVNNVWNG97 MIGEVVYQRA107 VMAVGSLTIN 117 EERSEVVDFS127 VPFVETGISV137 MVSRGTQVTG147 LSDKKFQRPH157 DYSPPFRFGT 167 VPNGSTERNI177 RNNYPYMHQY187 MTKFNQKGVE197 DALVSLKTGK207 LDAFIYDAAV 217 LNYKAGRDEG227 CKLVTIGSGY237 IFATTGYGIA247 LQKGSPWKRQ257 IDLALLQFVG 267 DGEMEELETL277 WLTGIC
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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 .A:116 or .A:128 or .A:129 or .A:130 or .A:131 or .A:132 or .A:241 or .A:242 or .A:243 or .A:263 or .A:266 or .A:271; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Gating mechanism and a modulatory niche of human GluN1-GluN2A NMDA receptors. Neuron. 2021 Aug 4;109(15):2443-2456.e5. | ||||
| REF 2 | 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 3 | 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 4 | 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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