Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T62820 | Target Info | |||
| Target Name | Metabotropic glutamate receptor 2 (mGluR2) | ||||
| Synonyms | mGLUR2; Group II metabotropic glutamate receptor; Glutamate receptor mGLU2; GPRC1B | ||||
| Target Type | Clinical trial Target | ||||
| Gene Name | GRM2 | ||||
| Biochemical Class | GPCR glutamate | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: ADX71149 | Ligand Info | |||||
| Structure Description | Cryo-EM structure of Gi-bound metabotropic glutamate receptor mGlu2 | PDB:7E9G | ||||
| Method | Electron microscopy | Resolution | 3.50 Å | Mutation | Yes | [1] |
| PDB Sequence |
KKVLTLEGDL
32 VLGGLFPVHQ42 KGGPAEDCGP52 VNEHRGIQRL62 EAMLFALDRI72 NRDPHLLPGV 82 RLGAHILDSC92 SKDTHALEQA102 LDFVRASLIT137 GVIGGSYSDV147 SIQVANLLRL 157 FQIPQISYAS167 TSAKLSDKSR177 YDYFARTVPP187 DFFQAKAMAE197 ILRFFNWTYV 207 STVASEGDYG217 ETGIEAFELE227 ARARNICVAT237 SEKVGRAMSR247 AAFEGVVRAL 257 LQKPSARVAV267 LFTRSEDARE277 LLAASQRLNA287 SFTWVASDGW297 GALESVVAGS 307 EGAAEGAITI317 ELASYPISDF327 ASYFQSLDPW337 NNSRNPWFRE347 FWEQRFRCSF 357 RQRDCAAHSL367 RAVPFEQESK377 IMFVVNAVYA387 MAHALHNMHR397 ALCPNTTRLC 407 DAMRPVNGRR417 LYKDFVLNVK427 FDAPFRPADT437 HNEVRFDRFG447 DGIGRYNIFT 457 YLRAGSGRYR467 YQKVGYWAEG477 LTLDTSLIPW487 ASPSAGPLPA497 SRCSEPCLQN 507 EVKSVQPGEV517 CCWLCIPCQP527 YEYRLDEFTC537 ADCGLGYWPN547 ASLTGCFELP 557 QEYIRWGDAW567 AVGPVTIACL577 GALATLFVLG587 VFVRHNATPV597 VKAAGRELCY 607 ILLGGVFLCY617 CMTFIFIAKP627 STAVCTLRRL637 GLGTAFSVCY647 SALLTKTNRI 657 ARIFGGAREG667 AQRPRFISPA677 SQVAICLALI687 SGQLLIVVAW697 LVVEAPGTGK 707 ETAPERREVV717 TLRCNHRDAS727 MLGSLAYNVL737 LIALCTLYAF747 KTRKCPENFN 757 EAKFIGFTMY767 TTCIIWLAFL777 PIFYVTSSDY787 RVQTTTMCVS797 VSLSGSVVLG 807 CLFAPKLHI
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| Ligand Name: [3H]LY341495 | Ligand Info | |||||
| Structure Description | CryoEM Structure of Full-Length mGlu2 in Inactive-State Bound to Antagonist LY341495 | PDB:7MTQ | ||||
| Method | Electron microscopy | Resolution | 3.65 Å | Mutation | No | [2] |
| PDB Sequence |
KVLTLEGDLV
33 LGGLFPVHQK43 PAEDCGPVNE55 HRGIQRLEAM65 LFALDRINRD75 PHLLPGVRLG 85 AHILDSCSKD95 THALEQALDF105 VRASLPTAIT137 GVIGGSYSDV147 SIQVANLLRL 157 FQIPQISYAS167 TSAKLSDKSR177 YDYFARTVPP187 DFFQAKAMAE197 ILRFFNWTYV 207 STVASEGDYG217 ETGIEAFELE227 ARARNICVAT237 SEKVGRAMSR247 AAFEGVVRAL 257 LQKPSARVAV267 LFTRSEDARE277 LLAASQRLNA287 SFTWVASDGW297 GALESVVAGS 307 EGAAEGAITI317 ELASYPISDF327 ASYFQSLDPW337 NNSRNPWFRE347 FWEQRFRCSF 357 RQRDCAAHSL367 RAVPFEQESK377 IMFVVNAVYA387 MAHALHNMHR397 ALCPNTTRLC 407 DAMRPVNGRR417 LYKDFVLNVK427 FDAPFRPADT437 HNEVRFDRFG447 DGIGRYNIFT 457 YLRAGSGRYR467 YQKVGYWAEG477 LTLDTSLIPW487 ASAGPLPASR499 CSEPCLQNEV 509 KSVQEVCCWL521 CIPCQYELDE534 FTCADCGLGW545 PNLTGCFELP557 QEYIRWDAWA 568 VGPVTIACLG578 ALATLFVLGV588 FVRHNATPVV598 KASGRELCYI608 LLGGVFLCYC 618 MTFIFIAKPS628 TAVCTLRRLG638 LGTAFSVCYS648 ALLTKTNRIA658 RSPASQVAIC 683 LALISGQLLI693 VVAWLVVEAP703 GTETAPERRE715 VVTLRCNHRD725 ASMLGSLAYN 735 VLLILCTLYA746 FKTRKCPENF756 NEAKFIGFTM766 YTTCIIWLAF776 LPIFYVTSSD 786 YRVQTTTMCV796 SVSLSGSVVL806 GCLFAPKLHI816 IL
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| Ligand Name: LY354740 | Ligand Info | |||||
| Structure Description | mGluR2 ECD and mGluR3 ECD with ligands | PDB:4XAQ | ||||
| Method | X-ray diffraction | Resolution | 2.21 Å | Mutation | No | [3] |
| PDB Sequence |
AKKVLTLEGD
31 LVLGGLFPVH41 QKGGPAEDCG51 PVNEHRGIQR61 LEAMLFALDR71 INRDPHLLPG 81 VRLGAHILDS91 CSKDTHALEQ101 ALDFVRASLT134 AITGVIGGSY144 SDVSIQVANL 154 LRLFQIPQIS164 YASTSAKLSD174 KSRYDYFART184 VPPDFFQAKA194 MAEILRFFNW 204 TYVSTVASEG214 DYGETGIEAF224 ELEARARNIS234 VATSEKVGRA244 MSRAAFEGVV 254 RALLQKPSAR264 VAVLFTRSED274 ARELLAASQR284 LNASFTWVAS294 DGWGALEEVV 304 AGSEGAAEGA314 ITIELASYPI324 SDFASYFQSL334 DPWNNSRNPW344 FREFWEQRFR 354 CSFRQRDCAA364 HSLRAVPFEQ374 ESKIMFVVNA384 VYAMAHALHN394 MHRALCPNTT 404 RLCDAMRPVN414 GRRLYKDFVL424 NVKFDAPFRP434 ADTHNEVRFD444 RFGDGIGRYN 454 IFTYLRAGSG464 RYRYQKVGYW474 AEGLTLDTSL484 IPW
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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 .40F or .40F2 or .40F3 or :340F;style chemicals stick;color identity;select .A:57 or .A:61 or .A:143 or .A:144 or .A:145 or .A:166 or .A:167 or .A:168 or .A:169 or .A:216 or .A:271 or .A:295 or .A:296 or .A:318 or .A:375 or .A:377; 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: 2-methoxy-6-propyl-N-(2-{4-[(1H-tetrazol-5-yl)methoxy]phenyl}ethyl)thieno[2,3-d]pyrimidin-4-amine | Ligand Info | |||||
| Structure Description | CryoEM Structure of mGlu2 - Gi Complex | PDB:7MTS | ||||
| Method | Electron microscopy | Resolution | 3.20 Å | Mutation | No | [2] |
| PDB Sequence |
KKVLTLEGDL
32 VLGGLFPVHQ42 KGGPAEDCGP52 VNEHRGIQRL62 EAMLFALDRI72 NRDPHLLPGV 82 RLGAHILDSC92 SKDTHALEQA102 LDFVRASTAI136 TGVIGGSYSD146 VSIQVANLLR 156 LFQIPQISYA166 STSAKLSDKS176 RYDYFARTVP186 PDFFQAKAMA196 EILRFFNWTY 206 VSTVASEGDY216 GETGIEAFEL226 EARARNICVA236 TSEKVGRAMS246 RAAFEGVVRA 256 LLQKPSARVA266 VLFTRSEDAR276 ELLAASQRLN286 ASFTWVASDG296 WGALESVVAG 306 SEGAAEGAIT316 IELASYPISD326 FASYFQSLDP336 WNNSRNPWFR346 EFWEQRFRCS 356 FRQRDCAAHS366 LRAVPFEQES376 KIMFVVNAVY386 AMAHALHNMH396 RALCPNTTRL 406 CDAMRPVNGR416 RLYKDFVLNV426 KFDAPFRPAD436 THNEVRFDRF446 GDGIGRYNIF 456 TYLRAGGRYR467 YQKVGYWAEG477 LTLDTSLIPW487 ASPSAGPLPA497 SRCSEPCLQN 507 EVKSVQPGEV517 CCWLCIPCQP527 YEYRLDEFTC537 ADCGLGYWPN547 ASLTGCFELP 557 QEYIRWGDAW567 AVGPVTIACL577 GALATLFVLG587 VFVRHNATPV597 VKASGRELCY 607 ILLGGVFLCY617 CMTFIFIAKP627 STAVCTLRRL637 GLGTAFSVCY647 SALLTKTNRI 657 ARIFGGAREG667 AQRPRFISPA677 SQVAICLALI687 SGQLLIVVAW697 LVVEAPGTGK 707 ETAPERREVV717 TLRCNHRDAS727 MLGSLAYNVL737 LIALCTLYAF747 KTRKCPENFN 757 EAKFIGFTMY767 TTCIIWLAFL777 PIFYVTSSDY787 RVQTTTMCVS797 VSLSGSVVLG 807 CLFAPKLHII817 LFQPQKNVVS827 HRA
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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 .ZQY or .ZQY2 or .ZQY3 or :3ZQY;style chemicals stick;color identity;select .A:623 or .A:639 or .A:640 or .A:643 or .A:647 or .A:720 or .A:724 or .A:728 or .A:731 or .A:732 or .A:735 or .A:736 or .A:739 or .A:769 or .A:770 or .A:773 or .A:776 or .A:780 or .A:794; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: (1~{s},2~{r},3~{s},4~{s},5~{r},6~{r})-2-Azanyl-3-[[3,4-Bis(Fluoranyl)phenyl]sulfanylmethyl]-4-Oxidanyl-Bicyclo[3.1.0]hexane-2,6-Dicarboxylic Acid | Ligand Info | |||||
| Structure Description | Metabotropic Glutamate Receptor in complex with antagonist (1~{S},2~{R},3~{S},4~{S},5~{R},6~{R})-2-azanyl-3-[[3,4-bis(fluoranyl)phenyl]sulfanylmethyl]-4-oxidanyl-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid | PDB:5KZQ | ||||
| Method | X-ray diffraction | Resolution | 2.80 Å | Mutation | No | [4] |
| PDB Sequence |
KVLTLEGDLV
33 LGGLFPVHQK43 PAEDCGPVNE55 HRGIQRLEAM65 LFALDRINRD75 PHLLPGVRLG 85 AHILDSCSKD95 THALEQALDF105 VRASLPTAIT137 GVIGGSYSDV147 SIQVANLLRL 157 FQIPQISYAS167 TSAKLSDKSR177 YDYFARTVPP187 DFFQAKAMAE197 ILRFFNWTYV 207 STVASEGDYG217 ETGIEAFELE227 ARARNICVAT237 SEKVGRAMSR247 AAFEGVVRAL 257 LQKPSARVAV267 LFTRSEDARE277 LLAASQRLNA287 SFTWVASDGW297 GALESVVAGS 307 EGAAEGAITI317 ELASYPISDF327 ASYFQSLDPW337 NNSRNPWFRE347 FWEQRFRCSF 357 RQRDCAAHSL367 RAVPFEQESK377 IMFVVNAVYA387 MAHALHNMHR397 ALCPNTTRLC 407 DAMRPVNGRR417 LYKDFVLNVK427 FDAPFRPADT437 HNEVRFDRFG447 DGIGRYNIFT 457 YLRAGGRYRY468 QKVGYWAEGL478 TLDTSLIPWA488 SPSAGPLPAS498 RCSEPCLQNE 508 VKSVQPGEVC518 CWLCIPCQPY528 EYRLDEFTCA538 DCGLGYWPNA548 SLT |
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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 .6YS or .6YS2 or .6YS3 or :36YS;style chemicals stick;color identity;select .A:57 or .A:61 or .A:143 or .A:144 or .A:145 or .A:166 or .A:167 or .A:168 or .A:169 or .A:188 or .A:216 or .A:270 or .A:271 or .A:272 or .A:273 or .A:295 or .A:296 or .A:375 or .A:377; 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,4s,5s,6s)-4-Aminospiro[bicyclo[3.1.0]hexane-2,1'-Cyclopropane]-4,6-Dicarboxylic Acid | Ligand Info | |||||
| Structure Description | mGluR2 ECD ligand complex | PDB:4XAS | ||||
| Method | X-ray diffraction | Resolution | 2.35 Å | Mutation | No | [3] |
| PDB Sequence |
KKVLTLEGDL
32 VLGGLFPVHQ42 KGGPAEDCGP52 VNEHRGIQRL62 EAMLFALDRI72 NRDPHLLPGV 82 RLGAHILDSC92 SKDTHALEQA102 LDFVRASTAI136 TGVIGGSYSD146 VSIQVANLLR 156 LFQIPQISYA166 STSAKLSDKS176 RYDYFARTVP186 PDFFQAKAMA196 EILRFFNWTY 206 VSTVASEGDY216 GETGIEAFEL226 EARARNISVA236 TSEKVGRAMS246 RAAFEGVVRA 256 LLQKPSARVA266 VLFTRSEDAR276 ELLAASQRLN286 ASFTWVASDG296 WGALEEVVAG 306 SEGAAEGAIT316 IELASYPISD326 FASYFQSLDP336 WNNSRNPWFR346 EFWEQRFRCS 356 FRQRDCAAHS366 LRAVPFEQES376 KIMFVVNAVY386 AMAHALHNMH396 RALCPNTTRL 406 CDAMRPVNGR416 RLYKDFVLNV426 KFDAPFRPAD436 THNEVRFDRF446 GDGIGRYNIF 456 TYLRAGGRYR467 YQKVGYWAEG477 LTLDTSLIPW487
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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 .40H or .40H2 or .40H3 or :340H;style chemicals stick;color identity;select .A:57 or .A:61 or .A:143 or .A:144 or .A:145 or .A:166 or .A:167 or .A:168 or .A:169 or .A:188 or .A:216 or .A:270 or .A:271 or .A:272 or .A:295 or .A:296 or .A:375 or .A:377; 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,2s,4r,5r,6r)-2-Amino-4-(1h-1,2,4-Triazol-3-Ylsulfanyl)bicyclo[3.1.0]hexane-2,6-Dicarboxylic Acid | Ligand Info | |||||
| Structure Description | mGlur2 with glutamate analog | PDB:5CNJ | ||||
| Method | X-ray diffraction | Resolution | 2.65 Å | Mutation | No | [5] |
| PDB Sequence |
AKKVLTLEGD
31 LVLGGLFPVH41 QKGGPAEDCG51 PVNEHRGIQR61 LEAMLFALDR71 INRDPHLLPG 81 VRLGAHILDS91 CSKDTHALEQ101 ALDFVRASLP133 TAITGVIGGS143 YSDVSIQVAN 153 LLRLFQIPQI163 SYASTSAKLS173 DKSRYDYFAR183 TVPPDFFQAK193 AMAEILRFFN 203 WTYVSTVASE213 GDYGETGIEA223 FELEARARNI233 SVATSEKVGR243 AMSRAAFEGV 253 VRALLQKPSA263 RVAVLFTRSE273 DARELLAASQ283 RLNASFTWVA293 SDGWGALESV 303 VAGSEGAAEG313 AITIELASYP323 ISDFASYFQS333 LDPWNNSRNP343 WFREFWEQRF 353 RCSFRQRDCA363 AHSLRAVPFE373 QESKIMFVVN383 AVYAMAHALH393 NMHRALCPNT 403 TRLCDAMRPV413 NGRRLYKDFV423 LNVKFDAPFR433 PADTHNEVRF443 DRFGDGIGRY 453 NIFTYLRAGS463 GRYRYQKVGY473 WAEGLTLDTS483 LIPWA
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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 .52Q or .52Q2 or .52Q3 or :352Q;style chemicals stick;color identity;select .A:57 or .A:61 or .A:143 or .A:144 or .A:145 or .A:166 or .A:167 or .A:168 or .A:169 or .A:216 or .A:270 or .A:271 or .A:272 or .A:273 or .A:295 or .A:296 or .A:375 or .A:377; 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 | Structures of G(i)-bound metabotropic glutamate receptors mGlu2 and mGlu4. Nature. 2021 Jun;594(7864):583-588. | ||||
| REF 2 | G-protein activation by a metabotropic glutamate receptor. Nature. 2021 Jul;595(7867):450-454. | ||||
| REF 3 | Synthesis and pharmacological characterization of C4-disubstituted analogs of 1S,2S,5R,6S-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylate: identification of a potent, selective metabotropic glutamate receptor agonist and determination of agonist-bound human mGlu2 and mGlu3 amino terminal domain structures. J Med Chem. 2015 Feb 26;58(4):1776-94. | ||||
| REF 4 | Discovery of (1S,2R,3S,4S,5R,6R)-2-Amino-3-[(3,4-difluorophenyl)sulfanylmethyl]-4-hydroxy-bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid Hydrochloride (LY3020371 HCl): A Potent, Metabotropic Glutamate 2/3 Receptor Antagonist with Antidepressant-Like Activity. J Med Chem. 2016 Dec 22;59(24):10974-10993. | ||||
| REF 5 | Synthesis and Pharmacological Characterization of C4-(Thiotriazolyl)-substituted-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylates. Identification of (1R,2S,4R,5R,6R)-2-Amino-4-(1H-1,2,4-triazol-3-ylsulfanyl)bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY2812223), a Highly Potent, Functionally Selective mGlu2 Receptor Agonist. J Med Chem. 2015 Sep 24;58(18):7526-48. | ||||
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