Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T20709 | Target Info | |||
| Target Name | Muscarinic acetylcholine receptor M4 (CHRM4) | ||||
| Synonyms | M4 receptor; CHRM4 | ||||
| Target Type | Successful Target | ||||
| Gene Name | CHRM4 | ||||
| Biochemical Class | GPCR rhodopsin | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: Tiotropium | Ligand Info | |||||
| Structure Description | Structure of the M4 muscarinic acetylcholine receptor (M4-mT4L) bound to tiotropium | PDB:5DSG | ||||
| Method | X-ray diffraction | Resolution | 2.60 Å | Mutation | Yes | [1] |
| PDB Sequence |
GPSSHNRYET
29 VEMVFIATVT39 GSLSLVTVVG49 NILVMLSIKV59 NRQLQTVNNY69 FLFSLACADL 79 IIGAFSMNLY89 TVYIIKGYWP99 LGAVVCDLWL109 ALDYVVSNAS119 VMNLLIISFD 129 RYFCVTKPLT139 YPARRTTKMA149 GLMIAAAWVL159 SFVLWAPAIL169 FWQFVVGKRT 179 VPDNQCFIQF189 LSNPAVTFGT199 AIAAFYLPVV209 IMTVLYIHIS219 LASRSRVNIF 1004 EMLRIDEEAE1021 KLFNQDVDAA1031 VRGILRNAKL1041 KPVYDSLDAV1051 RRAALINMVF 1061 QMGETGVAGF1071 TNSLRMLQQK1081 RWDEAAVNLA1091 KSRWYNQTPN1101 RAKRVITTFR 1111 TGTWDAYRKV398 TRTIFAILLA408 FILTWTPYNV418 MVLVNTFCQS428 CIPDTVWSIG 438 YWLCYVNSTI448 NPACYALCNA458 TFKKTFRHLL468 LC
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| Ligand Name: Adenosine | Ligand Info | |||||
| Structure Description | Cryo-EM structure of the human adenosine A1 receptor-Gi2-protein complex bound to its endogenous agonist and an allosteric ligand | PDB:7LD3 | ||||
| Method | Electron microscopy | Resolution | 3.20 Å | Mutation | No | [2] |
| PDB Sequence |
SISAFQAAYI
13 GIEVLIALVS23 VPGNVLVIWA33 VKVNQALRDA43 TFCFIVSLAV53 ADVAVGALVI 63 PLAILINIGP73 QTYFHTCLMV83 ACPVLILTQS93 SILALLAIAV103 DRYLRVKIPL 113 RYKMVVTPRR123 AAVAIAGCWI133 LSFVVGLTPM143 FGWNNLSAVE153 RAWAANGSMG 163 EPVIKCEFEK173 VISMEYMVYF183 NFFVWVLPPL193 LLMVLIYLEV203 FYLIRKQLNK 213 KYYGKELKIA233 KSLALILFLF243 ALSWLPLHIL253 NCITLFCPSC263 HKPSILTYIA 273 IFLTHGNSAM283 NPIVYAFRIQ293 KFRVTFLK
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Edetic acid | Ligand Info | |||||
| Structure Description | Structure of the M4 muscarinic acetylcholine receptor (M4-mT4L) bound to tiotropium | PDB:5DSG | ||||
| Method | X-ray diffraction | Resolution | 2.60 Å | Mutation | Yes | [1] |
| PDB Sequence |
GPSSHNRYET
29 VEMVFIATVT39 GSLSLVTVVG49 NILVMLSIKV59 NRQLQTVNNY69 FLFSLACADL 79 IIGAFSMNLY89 TVYIIKGYWP99 LGAVVCDLWL109 ALDYVVSNAS119 VMNLLIISFD 129 RYFCVTKPLT139 YPARRTTKMA149 GLMIAAAWVL159 SFVLWAPAIL169 FWQFVVGKRT 179 VPDNQCFIQF189 LSNPAVTFGT199 AIAAFYLPVV209 IMTVLYIHIS219 LASRSRVNIF 1004 EMLRIDEEAE1021 KLFNQDVDAA1031 VRGILRNAKL1041 KPVYDSLDAV1051 RRAALINMVF 1061 QMGETGVAGF1071 TNSLRMLQQK1081 RWDEAAVNLA1091 KSRWYNQTPN1101 RAKRVITTFR 1111 TGTWDAYRKV398 TRTIFAILLA408 FILTWTPYNV418 MVLVNTFCQS428 CIPDTVWSIG 438 YWLCYVNSTI448 NPACYALCNA458 TFKKTFRHLL468 LC
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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 .EDT or .EDT2 or .EDT3 or :3EDT;style chemicals stick;color identity;select .A:20 or .A:21 or .A:23; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: Oleic acid | Ligand Info | |||||
| Structure Description | Structure of the M4 muscarinic acetylcholine receptor (M4-mT4L) bound to tiotropium | PDB:5DSG | ||||
| Method | X-ray diffraction | Resolution | 2.60 Å | Mutation | Yes | [1] |
| PDB Sequence |
GPSSHNRYET
29 VEMVFIATVT39 GSLSLVTVVG49 NILVMLSIKV59 NRQLQTVNNY69 FLFSLACADL 79 IIGAFSMNLY89 TVYIIKGYWP99 LGAVVCDLWL109 ALDYVVSNAS119 VMNLLIISFD 129 RYFCVTKPLT139 YPARRTTKMA149 GLMIAAAWVL159 SFVLWAPAIL169 FWQFVVGKRT 179 VPDNQCFIQF189 LSNPAVTFGT199 AIAAFYLPVV209 IMTVLYIHIS219 LASRSRVNIF 1004 EMLRIDEEAE1021 KLFNQDVDAA1031 VRGILRNAKL1041 KPVYDSLDAV1051 RRAALINMVF 1061 QMGETGVAGF1071 TNSLRMLQQK1081 RWDEAAVNLA1091 KSRWYNQTPN1101 RAKRVITTFR 1111 TGTWDAYRKV398 TRTIFAILLA408 FILTWTPYNV418 MVLVNTFCQS428 CIPDTVWSIG 438 YWLCYVNSTI448 NPACYALCNA458 TFKKTFRHLL468 LC
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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:80 or .A:83 or .A:84 or .A:87 or .A:88 or .A:91 or .A:99 or .A:100 or .A:103 or .A:104 or .A:107 or .A:111; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: Iperoxo | Ligand Info | |||||
| Structure Description | An Agonist and PAM-bound Class A GPCR with Gi protein complex structure | PDB:7V68 | ||||
| Method | Electron microscopy | Resolution | 3.40 Å | Mutation | No | [3] |
| PDB Sequence |
TVEMVFIATV
38 TGSLSLVTVV48 GNILVMLSIK58 VNRQLQTVNN68 YFLFSLACAD78 LIIGAFSMNL 88 YTVYIIKGYW98 PLGAVVCDLW108 LALDYVVSNA118 SVMNLLIISF128 DRYFCVTKPL 138 TYPARRTTKM148 AGLMIAAAWV158 LSFVLWAPAI168 LFWQFVVGKR178 TVPDNQCFIQ 188 FLSNPAVTFG198 TAIAAFYLPV208 VIMTVLYIHI218 SLASRSMAAR394 ERKVTRTIFA 404 ILLAFILTWT414 PYNVMVLVNT424 FCQSCIPDTV434 WSIGYWLCYV444 NSTINPACYA 454 LCNATFKKTF464 RHLLLCQ
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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 .IXO or .IXO2 or .IXO3 or :3IXO;style chemicals stick;color identity;select .R:112 or .R:113 or .R:116 or .R:117 or .R:120 or .R:164 or .R:203 or .R:204 or .R:413 or .R:416 or .R:417 or .R:439 or .R:442 or .R:443; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: LY2119620 | Ligand Info | |||||
| Structure Description | An Agonist and PAM-bound Class A GPCR with Gi protein complex structure | PDB:7V68 | ||||
| Method | Electron microscopy | Resolution | 3.40 Å | Mutation | No | [3] |
| PDB Sequence |
TVEMVFIATV
38 TGSLSLVTVV48 GNILVMLSIK58 VNRQLQTVNN68 YFLFSLACAD78 LIIGAFSMNL 88 YTVYIIKGYW98 PLGAVVCDLW108 LALDYVVSNA118 SVMNLLIISF128 DRYFCVTKPL 138 TYPARRTTKM148 AGLMIAAAWV158 LSFVLWAPAI168 LFWQFVVGKR178 TVPDNQCFIQ 188 FLSNPAVTFG198 TAIAAFYLPV208 VIMTVLYIHI218 SLASRSMAAR394 ERKVTRTIFA 404 ILLAFILTWT414 PYNVMVLVNT424 FCQSCIPDTV434 WSIGYWLCYV444 NSTINPACYA 454 LCNATFKKTF464 RHLLLCQ
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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 .2CU or .2CU2 or .2CU3 or :32CU;style chemicals stick;color identity;select .R:89 or .R:92 or .R:96 or .R:180 or .R:186 or .R:187 or .R:190 or .R:191 or .R:193 or .R:423 or .R:426 or .R:427 or .R:432 or .R:433 or .R:435 or .R:436 or .R:439; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: {2-Amino-4-[3,5-bis(trifluoromethyl)phenyl]thiophen-3-yl}(4-chlorophenyl)methanone | Ligand Info | |||||
| Structure Description | Cryo-EM structure of the human adenosine A1 receptor-Gi2-protein complex bound to its endogenous agonist and an allosteric ligand | PDB:7LD3 | ||||
| Method | Electron microscopy | Resolution | 3.20 Å | Mutation | No | [2] |
| PDB Sequence |
SISAFQAAYI
13 GIEVLIALVS23 VPGNVLVIWA33 VKVNQALRDA43 TFCFIVSLAV53 ADVAVGALVI 63 PLAILINIGP73 QTYFHTCLMV83 ACPVLILTQS93 SILALLAIAV103 DRYLRVKIPL 113 RYKMVVTPRR123 AAVAIAGCWI133 LSFVVGLTPM143 FGWNNLSAVE153 RAWAANGSMG 163 EPVIKCEFEK173 VISMEYMVYF183 NFFVWVLPPL193 LLMVLIYLEV203 FYLIRKQLNK 213 KYYGKELKIA233 KSLALILFLF243 ALSWLPLHIL253 NCITLFCPSC263 HKPSILTYIA 273 IFLTHGNSAM283 NPIVYAFRIQ293 KFRVTFLK
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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 .XTD or .XTD2 or .XTD3 or :3XTD;style chemicals stick;color identity;select .R:15 or .R:18 or .R:19 or .R:22 or .R:242 or .R:245 or .R:246 or .R:275 or .R:276 or .R:279 or .R:280 or .R:282 or .R:283; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: Methyl 4-[4-(3-methyl-2-oxidanylidene-benzimidazol-1-yl)piperidin-1-yl]piperidine-1-carboxylate | Ligand Info | |||||
| Structure Description | Cry-EM structure of M4-c110-G protein complex | PDB:7V6A | ||||
| Method | Electron microscopy | Resolution | 3.60 Å | Mutation | No | [3] |
| PDB Sequence |
TVEMVFIATV
38 TGSLSLVTVV48 GNILVMLSIK58 VNRQLQTVNN68 YFLFSLACAD78 LIIGAFSMNL 88 YTVYIIKGYW98 PLGAVVCDLW108 LALDYVVSNA118 SVMNLLIISF128 DRYFCVTKPL 138 TYPARRTTKM148 AGLMIAAAWV158 LSFVLWAPAI168 LFWQFVVGKR178 TVPDNQCFIQ 188 FLSNPAVTFG198 TAIAAFYLPV208 VIMTVLYIHI218 SLASRSMAAR394 ERKVTRTIFA 404 ILLAFILTWT414 PYNVMVLVNT424 FCQSCIPDTV434 WSIGYWLCYV444 NSTINPACYA 454 LCNATFKKTF464 RHLLLCQ
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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 .5XI or .5XI2 or .5XI3 or :35XI;style chemicals stick;color identity;select .R:89 or .R:92 or .R:184 or .R:185 or .R:186 or .R:416 or .R:419 or .R:420 or .R:423 or .R:427 or .R:428 or .R:429 or .R:430 or .R:431 or .R:432 or .R:435 or .R:436 or .R:439; 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 | Crystal structures of the M1 and M4 muscarinic acetylcholine receptors. Nature. 2016 Mar 17;531(7594):335-40. | ||||
| REF 2 | Positive allosteric mechanisms of adenosine A(1) receptor-mediated analgesia. Nature. 2021 Sep;597(7877):571-576. | ||||
| REF 3 | The unconventional activation of the muscarinic acetylcholine receptor M4R by diverse ligands. Nat Commun. 2022 May 23;13(1):2855. | ||||
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