Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T42392 | Target Info | |||
| Target Name | Glutamate receptor AMPA 2 (GRIA2) | ||||
| Synonyms | Glutamate receptor ionotropic, AMPA 2; Glutamate receptor 2; GluRK2; GluRB; GluR2; GluR-K2; GluR-B; GluR-2; GluA2; AMPAselective glutamate receptor 2; AMPA-selective glutamate receptor 2 | ||||
| Target Type | Successful Target | ||||
| Gene Name | GRIA2 | ||||
| Biochemical Class | Glutamate-gated ion channel | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: TAK-653 | Ligand Info | |||||
| Structure Description | Crystal structure of the GluA2o LBD in complex with glutamate and TAK-653 | PDB:7F3O | ||||
| Method | X-ray diffraction | Resolution | 1.44 Å | Mutation | No | [1] |
| PDB Sequence |
GSNKTVVVTT
420 ILESPYVMMK430 KNHEMLEGNE440 RYEGYCVDLA450 AEIAKHCGFK460 YKLTIVGDGK 470 YGARDADTKI480 WNGMVGELVY490 GKADIAIAPL500 TITLVREEVI510 DFSKPFMSLG 520 ISIMIKKGTP653 IESAEDLSKQ663 TEIAYGTLDS673 GSTKEFFRRS683 KIAVFDKMWT 693 YMRSAEPSVF703 VRTTAEGVAR713 VRKSKGKYAY723 LLESTMNEYI733 EQRKPCDTMK 743 VGGNLDSKGY753 GIATPKGSSL763 RNAVNLAVLK773 LNEQGLLDKL783 KNKWWYDKGE 793 CG
|
|||||
|
|
||||||
| Ligand Name: Mibampator | Ligand Info | |||||
| Structure Description | Crystal structure of the GluA2o LBD in complex with glutamate and LY451395 | PDB:5YBG | ||||
| Method | X-ray diffraction | Resolution | 1.52 Å | Mutation | No | [2] |
| PDB Sequence |
NKTVVVTTIL
422 ESPYVMMKKN432 HEMLEGNERY442 EGYCVDLAAE452 IAKHCGFKYK462 LTIVGDGKYG 472 ARDADTKIWN482 GMVGELVYGK492 ADIAIAPLTI502 TLVREEVIDF512 SKPFMSLGIS 522 IMIKKGTPIE655 SAEDLSKQTE665 IAYGTLDSGS675 TKEFFRRSKI685 AVFDKMWTYM 695 RSAEPSVFVR705 TTAEGVARVR715 KSKGKYAYLL725 ESTMNEYIEQ735 RKPCDTMKVG 745 GNLDSKGYGI755 ATPKGSSLRN765 AVNLAVLKLN775 EQGLLDKLKN785 KWWYDKGECG 795
|
|||||
|
|
||||||
| Ligand Name: ZK-200775 | Ligand Info | |||||
| Structure Description | Crystal structure of the GluA2o LBD in complex with ZK200775 and Compound-2 | PDB:5ZG2 | ||||
| Method | X-ray diffraction | Resolution | 1.25 Å | Mutation | No | [3] |
| PDB Sequence |
KTVVVTTILE
423 SPYVMMKKNH433 EMLEGNERYE443 GYCVDLAAEI453 AKHCGFKYKL463 TIVGDGKYGA 473 RDADTKIWNG483 MVGELVYGKA493 DIAIAPLTIT503 LVREEVIDFS513 KPFMSLGISI 523 MIKKGTPIES656 AEDLSKQTEI666 AYGTLDSGST676 KEFFRRSKIA686 VFDKMWTYMR 696 SAEPSVFVRT706 TAEGVARVRK716 SKGKYAYLLE726 STMNEYIEQR736 KPCDTMKVGG 746 NLDSKGYGIA756 TPKGSSLRNA766 VNLAVLKLNE776 QGLLDKLKNK786 WWYDKGECG |
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ZK1 or .ZK12 or .ZK13 or :3ZK1;style chemicals stick;color identity;select .A:423 or .A:426 or .A:471 or .A:499 or .A:500 or .A:501 or .A:506 or .A:671 or .A:673 or .A:674 or .A:675 or .A:676 or .A:707 or .A:723 or .A:725 or .A:726 or .A:728 or .A:729 or .A:753; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: TAK-137 | Ligand Info | |||||
| Structure Description | Crystal structure of the GluA2o LBD in complex with glutamate and TAK-137 | PDB:5ZG3 | ||||
| Method | X-ray diffraction | Resolution | 1.65 Å | Mutation | No | [3] |
| PDB Sequence |
NKTVVVTTIL
422 ESPYVMMKKN432 HEMLEGNERY442 EGYCVDLAAE452 IAKHCGFKYK462 LTIVGDGKYG 472 ARDADTKIWN482 GMVGELVYGK492 ADIAIAPLTI502 TLVREEVIDF512 SKPFMSLGIS 522 IMIKKGTPIE655 SAEDLSKQTE665 IAYGTLDSGS675 TKEFFRRSKI685 AVFDKMWTYM 695 RSAEPSVFVR705 TTAEGVARVR715 KSKGKYAYLL725 ESTMNEYIEQ735 RKPCDTMKVG 745 GNLDSKGYGI755 ATPKGSSLRN765 AVNLAVLKLN775 EQGLLDKLKN785 KWWYDKGECG 795
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .9C6 or .9C62 or .9C63 or :39C6;style chemicals stick;color identity;select .A:502 or .A:515 or .A:516 or .A:517 or .A:518 or .A:750 or .A:751 or .A:752 or .A:775 or .A:780; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: Cmpda | Ligand Info | |||||
| Structure Description | Crystal Structure of iGluR2 Ligand Binding Domain with Symmetric Sulfonamide Containing Potentiator | PDB:3RNN | ||||
| Method | X-ray diffraction | Resolution | 1.75 Å | Mutation | No | [4] |
| PDB Sequence |
NKTVVVTTIL
12 ESPYVMMKKN22 HEMLEGNERY32 EGYCVDLAAE42 IAKHCGFKYK52 LTIVGDGKYG 62 ARDADTKIWN72 GMVGELVYGK82 ADIAIAPLTI92 TLVREEVIDF102 SKPFMSLGIS 112 IMIKKGTPIE122 SAEDLSKQTE132 IAYGTLDSGS142 TKEFFRRSKI152 AVFDKMWTYM 162 RSAEPSVFVR172 TTAEGVARVR182 KSKGKYAYLL192 ESTMNEYIEQ202 RKPCDTMKVG 212 GNLDSKGYGI222 ATPKGSSLGN232 AVNLAVLKLN242 EQGLLDKLKN252 KWWYDKGEC |
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .RNN or .RNN2 or .RNN3 or :3RNN;style chemicals stick;color identity;select .A:92 or .A:104 or .A:105 or .A:106 or .A:107 or .A:108 or .A:217 or .A:218 or .A:219 or .A:238 or .A:239 or .A:242; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: 3,3'-Benzene-1,4-Diylbis(4-Cyano-5-Ethylthiophene-2-Carboxylic Acid) | Ligand Info | |||||
| Structure Description | Crystal Structure of iGluR2 Ligand Binding Domain and Symmetrical Carboxyl Containing Potentiator | PDB:3RN8 | ||||
| Method | X-ray diffraction | Resolution | 1.70 Å | Mutation | No | [4] |
| PDB Sequence |
KTVVVTTILE
13 SPYVMMKKNH23 EMLEGNERYE33 GYCVDLAAEI43 AKHCGFKYKL53 TIVGDGKYGA 63 RDADTKIWNG73 MVGELVYGKA83 DIAIAPLTIT93 LVREEVIDFS103 KPFMSLGISI 113 MIKKGTPIES123 AEDLSKQTEI133 AYGTLDSGST143 KEFFRRSKIA153 VFDKMWTYMR 163 SAEPSVFVRT173 TAEGVARVRK183 SKGKYAYLLE193 STMNEYIEQR203 KPCDTMKVGG 213 NLDSKGYGIA223 TPKGSSLGNA233 VNLAVLKLNE243 QGLLDKLKNK253 WWYDKGEC |
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .RN8 or .RN82 or .RN83 or :3RN8;style chemicals stick;color identity;select .A:92 or .A:104 or .A:105 or .A:106 or .A:107 or .A:108 or .A:217 or .A:218 or .A:219 or .A:238 or .A:239 or .A:242 or .A:247; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: 9-(4-Tert-butylphenyl)-3,4-dihydropyrido[2,1-c][1,2,4]thiadiazine 2,2-dioxide | Ligand Info | |||||
| Structure Description | Crystal structure of the GluA2o LBD in complex with ZK200775 and Compound-2 | PDB:5ZG2 | ||||
| Method | X-ray diffraction | Resolution | 1.25 Å | Mutation | No | [3] |
| PDB Sequence |
KTVVVTTILE
423 SPYVMMKKNH433 EMLEGNERYE443 GYCVDLAAEI453 AKHCGFKYKL463 TIVGDGKYGA 473 RDADTKIWNG483 MVGELVYGKA493 DIAIAPLTIT503 LVREEVIDFS513 KPFMSLGISI 523 MIKKGTPIES656 AEDLSKQTEI666 AYGTLDSGST676 KEFFRRSKIA686 VFDKMWTYMR 696 SAEPSVFVRT706 TAEGVARVRK716 SKGKYAYLLE726 STMNEYIEQR736 KPCDTMKVGG 746 NLDSKGYGIA756 TPKGSSLRNA766 VNLAVLKLNE776 QGLLDKLKNK786 WWYDKGECG |
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .9C0 or .9C02 or .9C03 or :39C0;style chemicals stick;color identity;select .A:502 or .A:515 or .A:516 or .A:517 or .A:518 or .A:750 or .A:751 or .A:752 or .A:775; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: 2-[[2-[5-Methyl-3-(trifluoromethyl)pyrazol-1-yl]acetyl]amino]-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide | Ligand Info | |||||
| Structure Description | Crystal structure of the GluA2o LBD in complex with glutamate and HBT1 | PDB:5YBF | ||||
| Method | X-ray diffraction | Resolution | 1.50 Å | Mutation | No | [2] |
| PDB Sequence |
NKTVVVTTIL
422 ESPYVMMKKN432 HEMLEGNERY442 EGYCVDLAAE452 IAKHCGFKYK462 LTIVGDGKYG 472 ARDADTKIWN482 GMVGELVYGK492 ADIAIAPLTI502 TLVREEVIDF512 SKPFMSLGIS 522 IMIKKGTPIE655 SAEDLSKQTE665 IAYGTLDSGS675 TKEFFRRSKI685 AVFDKMWTYM 695 RSAEPSVFVR705 TTAEGVARVR715 KSKGKYAYLL725 ESTMNEYIEQ735 RKPCDTMKVG 745 GNLDSKGYGI755 ATPKGSSLRN765 AVNLAVLKLN775 EQGLLDKLKN785 KWWYDKGECG 795
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .8SR or .8SR2 or .8SR3 or :38SR;style chemicals stick;color identity;select .A:502 or .A:514 or .A:515 or .A:516 or .A:517 or .A:518 or .A:750 or .A:751 or .A:752 or .A:771 or .A:772 or .A:775; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| 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 GluA2 LBD in complex with GNE3419 | PDB:5H8S | ||||
| Method | X-ray diffraction | Resolution | 1.70 Å | Mutation | Yes | [5] |
| PDB Sequence |
NKTVVVTTIL
12 ESPYVMMKKN22 HEMLEGNERY32 EGYCVDLAAE42 IAKHCGFKYK52 LTIVGDGKYG 62 ARDADTKIWN72 GMVGELVYGK82 ADIAIAPLTI92 TLVREEVIDF102 SKPFMSLGIS 112 IMIKKGTPIE122 SAEDLSKQTE132 IAYGTLDSGS142 TKEFFRRSKI152 AVFDKMWTYM 162 RSAEPSVFVR172 TTAEGVARVR182 KSKGKYAYLL192 ESTMNEYIEQ202 RKPCDTMKVG 212 GNLDSKGYGI222 ATPKGSSLGN232 AVNLAVLKLS242 EQGLLDKLKN252 KWWYDKGEC |
|||||
|
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:104 or .A:105 or .A:106 or .A:107 or .A:108 or .A:217 or .A:218 or .A:219 or .A:239; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: N-Methyl-1-{3-[(Methylsulfonyl)amino]-2,4-Dioxo-7-(Trifluoromethyl)-1,2,3,4-Tetrahydroquinazolin-6-Yl}-1h-Imidazole-4-Carboxamide | Ligand Info | |||||
| Structure Description | Crystal Structure Analysis of a 6-Amino Quinazolinedione Sulfonamide bound to human GluR2 | PDB:3UA8 | ||||
| Method | X-ray diffraction | Resolution | 1.90 Å | Mutation | No | [6] |
| PDB Sequence |
TVVVTTILES
14 PYVMMKKNHE24 MLEGNERYEG34 YCVDLAAEIA44 KHCGFKYKLT54 IVGDGKYGAR 64 DADTKIWNGM74 VGELVYGKAD84 IAIAPLTITL94 VREEVIDFSK104 PFMSLGISIM 114 IKKGTPIESA124 EDLSKQTEIA134 YGTLDSGSTK144 EFFRRSKIAV154 FDKMWTYMRS 164 AEPSVFVRTT174 AEGVARVRKS184 KGKYAYLLES194 TMNEYIEQRK204 PCDTMKVGGN 214 LDSKGYGIAT224 PKGSSLRNAV234 NLAVLKLNEQ244 GLLDKLKNKW254 WYDKGEC |
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .08W or .08W2 or .08W3 or :308W;style chemicals stick;color identity;select .A:13 or .A:16 or .A:61 or .A:89 or .A:90 or .A:91 or .A:93 or .A:96 or .A:142 or .A:174 or .A:175 or .A:193 or .A:195 or .A:196 or .A:220; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: N-[6-(1h-Imidazol-1-Yl)-7-Nitro-2,4-Dioxo-1,4-Dihydroquinazolin-3(2h)-Yl]methanesulfonamide | Ligand Info | |||||
| Structure Description | Crystal Structure Analysis of a Quinazolinedione sulfonamide bound to human GluR2: A Novel Class of Competitive AMPA Receptor Antagonists with Oral Activity | PDB:3R7X | ||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | No | [7] |
| PDB Sequence |
NKTVVVTTIL
12 ESPYVMMKKN22 HEMLEGNERY32 EGYCVDLAAE42 IAKHCGFKYK52 LTIVGDGKYG 62 ARDADTKIWN72 GMVGELVYGK82 ADIAIAPLTI92 TLVREEVIDF102 SKPFMSLGIS 112 IMIKKGTPIE122 SAEDLSKQTE132 IAYGTLDSGS142 TKEFFRRSKI152 AVFDKMWTYM 162 RSAEPSVFVR172 TTAEGVARVR182 KSKGKYAYLL192 ESTMNEYIEQ202 RKPCDTMKVG 212 GNLDSKGYGI222 ATPKGSSLRN232 AVNLAVLKLN242 EQGLLDKLKN252 KWWYDKGEC |
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .QSN or .QSN2 or .QSN3 or :3QSN;style chemicals stick;color identity;select .A:13 or .A:16 or .A:61 or .A:89 or .A:90 or .A:91 or .A:93 or .A:96 or .A:142 or .A:174 or .A:195 or .A:196 or .A:220; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Strictly regulated agonist-dependent activation of AMPA-R is the key characteristic of TAK-653 for robust synaptic responses and cognitive improvement. Sci Rep. 2021 Jul 15;11(1):14532. | ||||
| REF 2 | HBT1, a Novel AMPA Receptor Potentiator with Lower Agonistic Effect, Avoided Bell-Shaped Response in In Vitro BDNF Production. J Pharmacol Exp Ther. 2018 Mar;364(3):377-389. | ||||
| REF 3 | TAK-137, an AMPA-R potentiator with little agonistic effect, has a wide therapeutic window. Neuropsychopharmacology. 2019 Apr;44(5):961-970. | ||||
| REF 4 | Structural and functional analysis of two new positive allosteric modulators of GluA2 desensitization and deactivation. Mol Pharmacol. 2011 Aug;80(2):267-80. | ||||
| REF 5 | 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 6 | 6-Amino quinazolinedione sulfonamides as orally active competitive AMPA receptor antagonists. Bioorg Med Chem Lett. 2012 Jan 15;22(2):996-9. | ||||
| REF 7 | Quinazolinedione sulfonamides: a novel class of competitive AMPA receptor antagonists with oral activity. Bioorg Med Chem Lett. 2011 Jun 1;21(11):3358-61. | ||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.