Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T99347 | Target Info | |||
| Target Name | Metabotropic glutamate receptor 5 (mGluR5) | ||||
| Synonyms | MGLUR5; GPRC1E | ||||
| Target Type | Clinical trial Target | ||||
| Gene Name | GRM5 | ||||
| Biochemical Class | GPCR glutamate | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: AFQ056 | Ligand Info | |||||
| Structure Description | Structure of the human class C GPCR metabotropic glutamate receptor 5 transmembrane domain in complex with the negative allosteric modulator mavoglurant | PDB:4OO9 | ||||
| Method | X-ray diffraction | Resolution | 2.60 Å | Mutation | Yes | [1] |
| PDB Sequence |
SPVQYLRWGD
577 PAPIAAVVFA587 CLGLLATLFV597 TVVFIIYRDT607 PVVKSSSREL617 CYIILAGICL 627 GYLCTFLIAK638 PKQIYCYLQR648 IGIGLSPAMS658 YSALVTKTYR668 AARILAMSKK 678 NIFEMLRIDE1011 GLRLKIYKDT1021 EGYYTIGIGH1031 LLTKSPSLNA1041 AKSELDKAIG 1051 RNTNGVITKD1061 EAEKLFNQDV1071 DAAVRGILRN1081 AKLKPVYDSL1091 DAVRRAALIN 1101 MVFQMGETGV1111 AGFTNSLRML1121 QQKRWDEAAV1131 NLAKSRWYNQ1141 TPNRAKRVIT 1151 TFRTGTWDAY1161 KISAAQLVIA697 FILICIQLGI707 IVALFIMEPP717 DIMVYLICNT 735 TNLGVVAPLG745 YNGLLILACT755 FYAFKTRNVP765 ANFNEAKYIA775 FTMYTTCIIW 785 LAFVPIYFGS795 NYKIITMCFS805 VSLSATVALG815 CMFVPKVYII825 LAKPERN |
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GLY624
3.547
ILE625
3.781
GLY628
4.118
ILE651
3.584
GLY652
4.620
SER654
3.671
PRO655
3.557
SER658
3.502
TYR659
3.238
VAL740
3.568
PRO743
3.406
LEU744
3.449
|
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| Ligand Name: [3H]LY341495 | Ligand Info | |||||
| Structure Description | Thermostabilised full length human mGluR5-5M with orthosteric antagonist, LY341495 | PDB:7FD9 | ||||
| Method | Electron microscopy | Resolution | 4.00 Å | Mutation | Yes | [2] |
| PDB Sequence |
RRVVAHMPGD
34 IIIGALFSVH44 HQPTVDKVHE54 RKCGAVREQY64 GIQRVEAMLH74 TLERINSDPT 84 LLPNITLGCE94 IRDSCWHSAV104 ALEQSIEFIR114 DSLISSKKPI143 VGVIGPGSSS 153 VAIQVQNLLQ163 LFNIPQIAYS173 ATSMDLSDKT183 LFKYFMRVVP193 SDAQQARAMV 203 DIVKRYNWTY213 VSAVHTEGNY223 GESGMEAFKD233 MSAKEGICIA243 HSYKIYSNAG 253 EQSFDKLLKK263 LTSHLPKARV273 VACFCEGMTV283 RGLLMAMRRL293 GLAGEFLLLG 303 SDGWADRYDV313 TDGYQREAVG323 GITIKLQSPD333 VKWFDDYYLK343 LRPETNLRNP 353 WFQEFWQHRF363 QCRLEGFPQE373 NSKYNKTCNS383 SLTLKTHHVQ393 DSKMGFVINA 403 IYSMAYGLHN413 MQMSLCPGYA423 GLCDAMKPID433 GRKLLESLMK443 TAFTGVSGDT 453 ILFDENGDSP463 GRYEIMNFKE473 MGKDYFDYIN483 VGSWDNGELK493 MDDDEVWSKK 503 SNIIRSVCSE513 PCEKGQIKVI523 RKGEVSCCWT533 CTPCKENEYV543 FDEYTCKACQ 553 LGSWPTDDLT563 GCDLIPVQYL573 RWGDPEPIAA583 VVFACLGLLA593 TLFVTVVFII 603 YRDTPVVKSS613 SRELCYIILA623 GICLGYLCTF633 CLIAKPKQIY643 CYLQRIGIGL 653 SPAMSYSALV663 TKTNRIARIL673 ACAQLVIAFI699 LICIQLGIIV709 ALFIMEPPDI 719 MHDYPSIREV729 YLICNTTNLG739 VVAPLGYNGL749 LILACTFYAF759 KTRNVPANFN 769 EAKYIAFAMY779 TTCIIWLAFV789 PIYFGSNYKA799 ITMCFSVSLS809 ATVLLGCMFV 819 PKVYIIL
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| Ligand Name: Oleic acid | Ligand Info | |||||
| Structure Description | Structure of the human class C GPCR metabotropic glutamate receptor 5 transmembrane domain in complex with the negative allosteric modulator mavoglurant | PDB:4OO9 | ||||
| Method | X-ray diffraction | Resolution | 2.60 Å | Mutation | Yes | [1] |
| PDB Sequence |
SPVQYLRWGD
577 PAPIAAVVFA587 CLGLLATLFV597 TVVFIIYRDT607 PVVKSSSREL617 CYIILAGICL 627 GYLCTFLIAK638 PKQIYCYLQR648 IGIGLSPAMS658 YSALVTKTYR668 AARILAMSKK 678 NIFEMLRIDE1011 GLRLKIYKDT1021 EGYYTIGIGH1031 LLTKSPSLNA1041 AKSELDKAIG 1051 RNTNGVITKD1061 EAEKLFNQDV1071 DAAVRGILRN1081 AKLKPVYDSL1091 DAVRRAALIN 1101 MVFQMGETGV1111 AGFTNSLRML1121 QQKRWDEAAV1131 NLAKSRWYNQ1141 TPNRAKRVIT 1151 TFRTGTWDAY1161 KISAAQLVIA697 FILICIQLGI707 IVALFIMEPP717 DIMVYLICNT 735 TNLGVVAPLG745 YNGLLILACT755 FYAFKTRNVP765 ANFNEAKYIA775 FTMYTTCIIW 785 LAFVPIYFGS795 NYKIITMCFS805 VSLSATVALG815 CMFVPKVYII825 LAKPERN |
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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 .OLA or .OLA2 or .OLA3 or :3OLA;style chemicals stick;color identity;select .A:568 or .A:569 or .A:570 or .A:581 or .A:584 or .A:585 or .A:588 or .A:589 or .A:592 or .A:633 or .A:636 or .A:637 or .A:638 or .A:645 or .A:702 or .A:705 or .A:706 or .A:709 or .A:712 or .A:713 or .A:729 or .A:737 or .A:741 or .A:744 or .A:745 or .A:748 or .A:749 or .A:751 or .A:752 or .A:782 or .A:785 or .A:786 or .A:789 or .A:793; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
SER568
4.034
PRO569
3.276
VAL570
3.209
ILE581
3.579
VAL584
3.677
VAL585
4.425
CYS588
3.654
LEU589
3.830
LEU592
4.176
PHE633
3.506
ILE636
3.245
ALA637
3.405
LYS638
4.050
TYR645
3.445
CYS702
4.998
LEU705
4.786
GLY706
4.530
|
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Cholesterol hemisuccinate | Ligand Info | |||||
| Structure Description | Thermostabilised full length human mGluR5-5M bound with L-quisqualic acid | PDB:7FD8 | ||||
| Method | Electron microscopy | Resolution | 3.80 Å | Mutation | Yes | [2] |
| PDB Sequence |
RRVVAHMPGD
34 IIIGALFSVH44 HQPTVDKVHE54 RKCGAVREQY64 GIQRVEAMLH74 TLERINSDPT 84 LLPNITLGCE94 IRDSCWHSAV104 ALEQSIEFIR114 DSLKPIVGVI147 GPGSSSVAIQ 157 VQNLLQLFNI167 PQIAYSATSM177 DLSDKTLFKY187 FMRVVPSDAQ197 QARAMVDIVK 207 RYNWTYVSAV217 HTEGNYGESG227 MEAFKDMSAK237 EGICIAHSYK247 IYSNAGEQSF 257 DKLLKKLTSH267 LPKARVVACF277 CEGMTVRGLL287 MAMRRLGLAG297 EFLLLGSDGW 307 ADRYDVTDGY317 QREAVGGITI327 KLQSPDVKWF337 DDYYLKLRPE347 TNLRNPWFQE 357 FWQHRFQCRL367 EGFPQENSKY377 NKTCNSSLTL387 KTHHVQDSKM397 GFVINAIYSM 407 AYGLHNMQMS417 LCPGYAGLCD427 AMKPIDGRKL437 LESLMKTAFT447 GVSGDTILFD 457 ENGDSPGRYE467 IMNFKEMGKD477 YFDYINVGSW487 DNGELKMDDD497 EVWSKKSNII 507 RSVCSEPCEK517 GQIKVIRKGE527 VSCCWTCTPC537 KENEYVFDEY547 TCKACQLGSW 557 PTDDLTGCDL567 IPVQYLRWGD577 PEPIAAVVFA587 CLGLLATLFV597 TVVFIIYRDT 607 PVVKSSSREL617 CYIILAGICL627 GYLCTFCLIA637 KPKQIYCYLQ647 RIGIGLSPAM 657 SYSALVTKTN667 RIARISACAQ693 LVIAFILICI703 QLGIIVALFI713 MEPPDIMHDY 723 PSIREVYLIC733 NTTNLGVVAP743 LGYNGLLILA753 CTFYAFKTRN763 VPANFNEAKY 773 IAFAMYTTCI783 IWLAFVPIYF793 GSNYKAITMC803 FSVSLSATVL813 LGCMFVPKVY 823 IILA
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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 .Y01 or .Y012 or .Y013 or :3Y01;style chemicals stick;color identity;select .A:574 or .A:575 or .A:581 or .A:584 or .A:585 or .A:588 or .A:630 or .A:633 or .A:643; 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 6971145 | Ligand Info | |||||
| Structure Description | Metabotropic Glutamate Receptor 5 Extracellular Domain in Complex with Nb43 and L-quisqualic acid | PDB:6N50 | ||||
| Method | X-ray diffraction | Resolution | 3.75 Å | Mutation | No | [3] |
| PDB Sequence |
RRVVAHMPGD
34 IIIGALFSVH44 HQPTVDKVHE54 RKCGAVREQY64 GIQRVEAMLH74 TLERINSDPT 84 LLPNITLGCE94 IRDSCWHSAV104 ALEQSIEFIR114 DSKPIVGVIG148 PGSSSVAIQV 158 QNLLQLFNIP168 QIAYSATSMD178 LSDKTLFKYF188 MRVVPSDAQQ198 ARAMVDIVKR 208 YNWTYVSAVH218 TEGNYGESGM228 EAFKDMSAKE238 GICIAHSYKI248 YSNAGEQSFD 258 KLLKKLTSHL268 PKARVVACFC278 EGMTVRGLLM288 AMRRLGLAGE298 FLLLGSDGWA 308 DRYDVTDGYQ318 REAVGGITIK328 LQSPDVKWFD338 DYYLKLRPET348 NHRNPWFQEF 358 WQHRFQCRLE368 GFPQENSKYN378 KTCNSSLTLK388 THHVQDSKMG398 FVINAIYSMA 408 YGLHNMQMSL418 CPGYAGLCDA428 MKPIDGRKLL438 ESLMKTNFTG448 VSGDTILFDE 458 NGDSPGRYEI468 MNFKEMGKDY478 FDYINVGSWD488 NGELKMDDDE498 VWSNIIRSVC 511 SEPCEKGQIK521 VIRKGEVSCC531 WTCTPCKENE541 YVFDEYTCKA551 CQLGSWPTDD 561 LTGCDLIP
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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 .QUS or .QUS2 or .QUS3 or :3QUS;style chemicals stick;color identity;select .A:64 or .A:68 or .A:100 or .A:150 or .A:151 or .A:152 or .A:173 or .A:174 or .A:175 or .A:176 or .A:195 or .A:223 or .A:279 or .A:280 or .A:305 or .A:306 or .A:310 or .A:396; 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: 3-Chloro-5-[6-(5-Fluoropyridin-2-Yl)pyrimidin-4-Yl]benzonitrile | Ligand Info | |||||
| Structure Description | Structure of the human class C GPCR metabotropic glutamate receptor 5 transmembrane domain in complex with the negative allosteric modulator 3-chloro-5-[6-(5-fluoropyridin-2-yl)pyrimidin-4-yl]benzonitrile - (HTL14242) | PDB:5CGD | ||||
| Method | X-ray diffraction | Resolution | 2.60 Å | Mutation | Yes | [4] |
| PDB Sequence |
SPVQYLRWGD
577 PAPIAAVVFA587 CLGLLATLFV597 TVVFIIYRDT607 PVVKSSSREL617 CYIILAGICL 627 GYLCTFCLIA637 KPKQIYCYLQ647 RIGIGLSPAM657 SYSALVTKTY667 RAARILAMSK 677 KNIFEMLRID1010 EGLRLKIYKD1020 TEGYYTIGIG1030 HLLTKSPSLN1040 AAKSELDKAI 1050 GRNTNGVITK1060 DEAEKLFNQD1070 VDAAVRGILR1080 NAKLKPVYDS1090 LDAVRRAALI 1100 NMVFQMGETG1110 VAGFTNSLRM1120 LQQKRWDEAA1130 VNLAKSRWYN1140 QTPNRAKRVI 1150 TTFRTGTWDA1160 YKISACAQLV695 IAFILICIQL705 GIIVALFIME715 PPDIMVYLIC 733 NTTNLGVVAP743 LGYNGLLILA753 CTFYAFKTRN763 VPANFNEAKY773 IAFTMYTTCI 783 IWLAFVPIYF793 GSNYKIITMC803 FSVSLSATVA813 LGCMFVPKVY823 IILAKPER |
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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 .51E or .51E2 or .51E3 or :351E;style chemicals stick;color identity;select .A:621 or .A:624 or .A:625 or .A:628 or .A:631 or .A:650 or .A:651 or .A:654 or .A:655 or .A:658 or .A:659 or .A:740 or .A:744 or .A:784 or .A:785 or .A:788 or .A:802 or .A:805 or .A:806 or .A:809 or .A:810 or .A:813; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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ILE621
4.879
GLY624
3.302
ILE625
3.155
GLY628
3.774
CYS631
4.244
GLY650
3.963
ILE651
3.670
SER654
3.382
PRO655
3.399
SER658
3.164
TYR659
3.299
|
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| Ligand Name: Cysteine-S-Acetamide | Ligand Info | |||||
| Structure Description | Structure of the human class C GPCR metabotropic glutamate receptor 5 transmembrane domain in complex with the negative allosteric modulator mavoglurant | PDB:4OO9 | ||||
| Method | X-ray diffraction | Resolution | 2.60 Å | Mutation | Yes | [1] |
| PDB Sequence |
SPVQYLRWGD
577 PAPIAAVVFA587 CLGLLATLFV597 TVVFIIYRDT607 PVVKSSSREL617 CYIILAGICL 627 GYLCTFLIAK638 PKQIYCYLQR648 IGIGLSPAMS658 YSALVTKTYR668 AARILAMSKK 678 NIFEMLRIDE1011 GLRLKIYKDT1021 EGYYTIGIGH1031 LLTKSPSLNA1041 AKSELDKAIG 1051 RNTNGVITKD1061 EAEKLFNQDV1071 DAAVRGILRN1081 AKLKPVYDSL1091 DAVRRAALIN 1101 MVFQMGETGV1111 AGFTNSLRML1121 QQKRWDEAAV1131 NLAKSRWYNQ1141 TPNRAKRVIT 1151 TFRTGTWDAY1161 KISAAQLVIA697 FILICIQLGI707 IVALFIMEPP717 DIMVYLICNT 735 TNLGVVAPLG745 YNGLLILACT755 FYAFKTRNVP765 ANFNEAKYIA775 FTMYTTCIIW 785 LAFVPIYFGS795 NYKIITMCFS805 VSLSATVALG815 CMFVPKVYII825 LAKPERN |
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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 .YCM or .YCM2 or .YCM3 or :3YCM;style chemicals stick;color identity;select .A:630 or .A:631 or .A:632 or .A:633 or .A:635 or .A:636 or .A:637 or .A:643 or .A:646 or .A:647 or .A:689 or .A:690 or .A:692 or .A:693 or .A:694 or .A:695 or .A:731; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 3-Chloro-4-Fluoro-5-[6-(1h-Pyrazol-1-Yl)pyrimidin-4-Yl]benzonitrile | Ligand Info | |||||
| Structure Description | Structure of the human class C GPCR metabotropic glutamate receptor 5 transmembrane domain in complex with the negative allosteric modulator 3-chloro-4-fluoro-5-[6-(1H-pyrazol-1-yl)pyrimidin-4-yl]benzonitrile | PDB:5CGC | ||||
| Method | X-ray diffraction | Resolution | 3.10 Å | Mutation | Yes | [4] |
| PDB Sequence |
SPVQYLRWGD
577 PAPIAAVVFA587 CLGLLATLFV597 TVVFIIYRDT607 PVVKSSSREL617 CYIILAGICL 627 GYLCTFCLIA637 KPKQIYCYLQ647 RIGIGLSPAM657 SYSALVTKTY667 RAARILAMSK 677 KNIFEMLRID1010 EGLRLKIYKD1020 TEGYYTIGIG1030 HLLTKSPSLN1040 AAKSELDKAI 1050 GRNTNGVITK1060 DEAEKLFNQD1070 VDAAVRGILR1080 NAKLKPVYDS1090 LDAVRRAALI 1100 NMVFQMGETG1110 VAGFTNSLRM1120 LQQKRWDEAA1130 VNLAKSRWYN1140 QTPNRAKRVI 1150 TTFRTGTWDA1160 YKISACAQLV695 IAFILICIQL705 GIIVALFIME715 PPDIMVYLIC 733 NTTNLGVVAP743 LGYNGLLILA753 CTFYAFKTRN763 VPANFNEAKY773 IAFTMYTTCI 783 IWLAFVPIYF793 GSNYKIITMC803 FSVSLSATVA813 LGCMFVPKVY823 IILAKPERN |
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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 .51D or .51D2 or .51D3 or :351D;style chemicals stick;color identity;select .A:624 or .A:625 or .A:628 or .A:631 or .A:650 or .A:651 or .A:654 or .A:655 or .A:658 or .A:659 or .A:740 or .A:744 or .A:784 or .A:785 or .A:788 or .A:802 or .A:805 or .A:806 or .A:809 or .A:810 or .A:813; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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GLY624
3.358
ILE625
3.662
GLY628
3.482
CYS631
4.057
GLY650
3.874
ILE651
3.523
SER654
3.535
PRO655
3.342
SER658
3.662
TYR659
3.873
VAL740
3.894
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Structure of class C GPCR metabotropic glutamate receptor 5 transmembrane domain. Nature. 2014 Jul 31;511(7511):557-62. | ||||
| REF 2 | Agonists and allosteric modulators promote signaling from different metabotropic glutamate receptor 5 conformations. Cell Rep. 2021 Aug 31;36(9):109648. | ||||
| REF 3 | Structural insights into the activation of metabotropic glutamate receptors. Nature. 2019 Feb;566(7742):79-84. | ||||
| REF 4 | Fragment and Structure-Based Drug Discovery for a Class C GPCR: Discovery of the mGlu5 Negative Allosteric Modulator HTL14242 (3-Chloro-5-[6-(5-fluoropyridin-2-yl)pyrimidin-4-yl]benzonitrile). J Med Chem. 2015 Aug 27;58(16):6653-64. | ||||
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