Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T99338 | Target Info | |||
| Target Name | Stimulator of interferon genes protein (TMEM173) | ||||
| Synonyms | Mediator of IRF3 activation; Endoplasmic reticulum interferon stimulator; ERIS | ||||
| Target Type | Clinical trial Target | ||||
| Gene Name | TMEM173 | ||||
| Biochemical Class | TMEM173 family | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: Vadimezan | Ligand Info | |||||
| Structure Description | Crystal structure of hSTING(group2) in complex with DMXAA | PDB:4QXO | ||||
| Method | X-ray diffraction | Resolution | 1.88 Å | Mutation | Yes | [1] |
| PDB Sequence |
SVAHGLAWSY
163 YIGYLRLILP173 ELQARIRTYN183 QHYNNLLRGA193 VSQRLYILLP203 LDCGVPDNLS 213 MADPNIRFRD223 MLPQQNIDRA233 GIKNRVYSNS243 VYELLENGQR253 AGTCVLEYAT 263 PLQTLFAMSQ273 YSQAGFSRED283 RLEQAKLFCR293 TLEDILADAP303 ESQNNCRLIA 313 YQEPADDSSF323 SLSQEVLRHL333 RQ
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| Ligand Name: L-serine-O-phosphate | Ligand Info | |||||
| Structure Description | phospho-STING binding to adaptor protein complex-1 | PDB:7R4H | ||||
| Method | Electron microscopy | Resolution | 2.34 Å | Mutation | Yes | [2] |
| PDB Sequence |
QEPELLIG
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| Ligand Name: (2R,5R,7R,8R,10R,12aR,14R,15aS,16R)-7-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)-16-hydroxy-14-[(pyrimidin-4-yl)oxy]-2,10-disulfanyldecahydro-2H,10H-5,8-methano-2lambda~5~,10lambda~5~-cyclopenta[l][1,3,6,9,11,2,10]pentaoxadiphosphacyclotetradecine-2,10-dione | Ligand Info | |||||
| Structure Description | Structure of hSTING in complex with novel carbocyclic pyrimidine CDN-3 | PDB:7KW1 | ||||
| Method | X-ray diffraction | Resolution | 1.80 Å | Mutation | No | [3] |
| PDB Sequence |
NFNVAHGLAW
161 SYYIGYLRLI171 LPELQARIRT181 YNQHYNNLLR191 GAVSQRLYIL201 LPLDCGVPDN 211 LSMADPNIRF221 LDKLPQQTGD231 RAGIKDRVYS241 NSIYELLENG251 QRAGTCVLEY 261 ATPLQTLFAM271 SQYSQAGFSR281 EDRLEQAKLF291 CRTLEDILAD301 APESQNNCRL 311 IAYQESFSLS326 QEVLRHLRQ
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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 .X4M or .X4M2 or .X4M3 or :3X4M;style chemicals stick;color identity;select .A:159 or .A:162 or .A:163 or .A:166 or .A:167 or .A:232 or .A:235 or .A:238 or .A:239 or .A:240 or .A:260 or .A:261 or .A:263 or .A:264 or .A:267; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: (2R,5R,7R,8R,10R,12aR,14R,15aS,16R)-7-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)-16-hydroxy-14-[(pyrimidin-4-yl)amino]-2,10-disulfanyldecahydro-2H,10H-5,8-methano-2lambda~5~,10lambda~5~-cyclopenta[l][1,3,6,9,11,2,10]pentaoxadiphosphacyclotetradecine-2,10-dione | Ligand Info | |||||
| Structure Description | Structure of hSTING in complex with novel carbocyclic pyrimidine CDN 1 | PDB:7KVX | ||||
| Method | X-ray diffraction | Resolution | 2.48 Å | Mutation | No | [3] |
| PDB Sequence |
NFNVAHGLAW
161 SYYIGYLRLI171 LPELQARIRT181 YNQHYNNLLR191 GAVSQRLYIL201 LPLDCGVPDN 211 LSMADPNIRF221 LDKLPQQTGD231 RAGIKDRVYS241 NSIYELLENG251 QRAGTCVLEY 261 ATPLQTLFAM271 SQYSQAGFSR281 EDRLEQAKLF291 CRTLEDILAD301 APESQNNCRL 311 IAYQEPSFSL325 SQEVLRHLRQ335 E
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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 .X5J or .X5J2 or .X5J3 or :3X5J;style chemicals stick;color identity;select .A:159 or .A:162 or .A:163 or .A:166 or .A:167 or .A:232 or .A:238 or .A:239 or .A:240 or .A:260 or .A:261 or .A:263 or .A:264 or .A:267; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: Cgamp | Ligand Info | |||||
| Structure Description | Crystal structure of STING in complex with cGAMP | PDB:4KSY | ||||
| Method | X-ray diffraction | Resolution | 1.88 Å | Mutation | Yes | [4] |
| PDB Sequence |
NFNVAHGLAW
161 SYYIGYLRLI171 LPELQARIRT181 YNQHYNNLLR191 GAVSQRLYIL201 LPLDCGVPDN 211 LSMADPNIRF221 LDKLPQQTGD231 RAGIKDRVYS241 NSIYELLENG251 QRAGTCVLEY 261 ATPLQTLFAM271 SQYSQAGFSR281 EDRLEQAKLF291 CRTLEDILAD301 APESQNNCRL 311 IAYQEPSFSL325 SQEVLRHLRQ335 E
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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 .1SY or .1SY2 or .1SY3 or :31SY;style chemicals stick;color identity;select .A:159 or .A:162 or .A:163 or .A:166 or .A:167 or .A:232 or .A:235 or .A:238 or .A:239 or .A:240 or .A:260 or .A:261 or .A:263 or .A:264 or .A:267; 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: 3'2'-Cgamp | Ligand Info | |||||
| Structure Description | Crystal structure of human STING in complex with 3'2'-cGAMP | PDB:5BQX | ||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [5] |
| PDB Sequence |
NFNVAHGLAW
161 SYYIGYLRLI171 LPELQARIRT181 YNQHYNRGAV194 SQRLYILLPL204 DCGVPDNLSM 214 ADPNIRFLDK224 LPQQTGDRAG234 IKDRVYSNSI244 YELLENGQRA254 GTCVLEYATP 264 LQTLFAMSQY274 SQAGFSREDR284 LEQAKLFCRT294 LEDILADAPE304 SQNNCRLIAY 314 QEPSFSLSQE328 VLRHLRQE
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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 .4UR or .4UR2 or .4UR3 or :34UR;style chemicals stick;color identity;select .A:162 or .A:163 or .A:166 or .A:167 or .A:232 or .A:235 or .A:238 or .A:239 or .A:240 or .A:241 or .A:242 or .A:260 or .A:262 or .A:263 or .A:264 or .A:267; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: Cyclic di-AMP | Ligand Info | |||||
| Structure Description | Human Stimulator of Interferon Genes | PDB:6CY7 | ||||
| Method | X-ray diffraction | Resolution | 2.20 Å | Mutation | No | [6] |
| PDB Sequence |
NVAHGLAWSY
163 YIGYLRLILP173 ELQARIRTYN183 QHAVSQRLYI200 LLPLDCGVPD210 NLSMADPNIR 220 FLDKLPQQTA230 DRAGIKDRVY240 SNSIYELLEN250 GQRAGTCVLE260 YATPLQTLFA 270 MSQYSQAGFS280 REDRLEQAKL290 FCRTLEDILA300 DAPESQNNCR310 LIAYQEPADD 320 SSFSLSQEVL330 RHLRQEE
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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 .2BA or .2BA2 or .2BA3 or :32BA;style chemicals stick;color identity;select .A:162 or .A:163 or .A:166 or .A:167 or .A:232 or .A:238 or .A:239 or .A:240 or .A:241 or .A:260 or .A:263 or .A:264; 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: 2'3'-cyclic-GMP-2'F-2'dAMP | Ligand Info | |||||
| Structure Description | Crystal structure of human wild type STING in complex with 2'3'-cyclic-GMP-2'F-2'dAMP | PDB:6S27 | ||||
| Method | X-ray diffraction | Resolution | 2.80 Å | Mutation | No | [7] |
| PDB Sequence |
NVAHGLAWSY
163 YIGYLRLILP173 ELQARIRTYN183 QHYNAVSQRL198 YILLPLDCGV208 PDNLSMADPN 218 IRFLDKLPQQ228 TGDRAGIKDR238 VYSNSIYELL248 ENGQRAGTCV258 LEYATPLQTL 268 FAMSQYSQAG278 FSREDRLEQA288 KLFCRTLEDI298 LADAPESQNN308 CRLIAYQEFS 324 LSQEVLRHLR334 QE
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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 .KT8 or .KT82 or .KT83 or :3KT8;style chemicals stick;color identity;select .A:159 or .A:162 or .A:163 or .A:164 or .A:165 or .A:166 or .A:167 or .A:232 or .A:235 or .A:238 or .A:239 or .A:240 or .A:241 or .A:260 or .A:261 or .A:262 or .A:263 or .A:264 or .A:267; 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-[(1-ethyl-3-methyl-1H-pyrazole-5-carbonyl)amino]-1-[(2R)-2-hydroxy-2-phenylethyl]-1H-benzimidazole-5-carboxamide | Ligand Info | |||||
| Structure Description | amidobenzimidazole (ABZI) STING agonists | PDB:6DXG | ||||
| Method | X-ray diffraction | Resolution | 1.91 Å | Mutation | No | [8] |
| PDB Sequence |
FNVAHGLAWS
162 YYIGYLRLIL172 PELQARIRTY182 NQHYNNLLRG192 AVSQRLYILL202 PLDCGVPDNL 212 SMADPNIRFL222 DKLPQQVYSN242 SIYELLENGQ252 RAGTCVLEYA262 TPLQTLFAMS 272 QYSQAGFSRE282 DRLEQAKLFC292 RTLEDILADA302 PESQNNCRLI312 AYQEPAFSLS 326 QEVLRHLRQE336 EKEEVTV
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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 .HGJ or .HGJ2 or .HGJ3 or :3HGJ;style chemicals stick;color identity;select .A:158 or .A:159 or .A:160 or .A:162 or .A:163 or .A:166 or .A:167 or .A:170 or .A:239 or .A:240 or .A:241 or .A:242 or .A:260 or .A:263 or .A:264 or .A:267 or .A:291; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: STING agonist-4 | Ligand Info | |||||
| Structure Description | Linked amidobenzimidazole STING agonist | PDB:6DXL | ||||
| Method | X-ray diffraction | Resolution | 2.45 Å | Mutation | No | [8] |
| PDB Sequence |
FNVAHGLAWS
162 YYIGYLRLIL172 PELQARIRTY182 NQHYNNLLRG192 AVSQRLYILL202 PLDCGVPDNL 212 SMADPNIRFL222 DKLPQQYSNS243 IYELLENGQR253 AGTCVLEYAT263 PLQTLFAMSQ 273 YSQAGFSRED283 RLEQAKLFCR293 TLEDILADAP303 ESQNNCRLIA313 YQEPADFSLS 326 QEVLRHLRQE336 EKEEVTV
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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 .HG4 or .HG42 or .HG43 or :3HG4;style chemicals stick;color identity;select .A:158 or .A:159 or .A:162 or .A:163 or .A:166 or .A:167 or .A:171 or .A:240 or .A:241 or .A:242 or .A:260 or .A:263 or .A:264 or .A:267 or .A:291; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 4,5-difluoro-2-{[6-(1H-imidazol-1-yl)pyridazine-3-carbonyl]amino}benzoic acid | Ligand Info | |||||
| Structure Description | Crystal Structure of Human STING CTD complex with SR-717 | PDB:6XNP | ||||
| Method | X-ray diffraction | Resolution | 1.77 Å | Mutation | No | [9] |
| PDB Sequence |
SVAHGLAWSY
163 YIGYLRLILP173 ELQARIRTYN183 QHYNNLLRGA193 VSQRLYILLP203 LDCGVPDNLS 213 MADPNIRFLD223 KLPQQTGDRA233 GIKDRVYSNS243 IYELLENGQR253 AGTCVLEYAT 263 PLQTLFAMSQ273 YSGFSREDRL285 EQAKLFCRTL295 EDILADAPES305 QNNCRLIAYQ 315 EPFSLSQEVL330 RHLRQE
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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 .V67 or .V672 or .V673 or :3V67;style chemicals stick;color identity;select .A:159 or .A:162 or .A:163 or .A:166 or .A:167 or .A:232 or .A:238 or .A:239 or .A:240 or .A:241 or .A:242 or .A:260 or .A:263 or .A:264; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: (3S,4S)-2-(4-tert-butylphenyl)-3-(4-methoxyphenyl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid | Ligand Info | |||||
| Structure Description | Crystal structure of human STING (G230A, H232R, R293Q) in complex with Compound 1 | PDB:6MX3 | ||||
| Method | X-ray diffraction | Resolution | 1.36 Å | Mutation | Yes | [10] |
| PDB Sequence |
SVAHGLAWSY
163 YIGYLRLILP173 ELQARIRTYN183 QHYNNLLRGA193 VSQRLYILLP203 LDCGVPDNLD 216 PNIRFLDKLP226 QSNSIYELLE249 NGQRAGTCVL259 EYATPLQTLF269 AMSQYSQAGF 279 SREDRLEQAK289 LFCQTLEDIL299 ADAPESQNNC309 RLIAYQEPSF323 SLSQEVLRHL 333 RQE
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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 .K5P or .K5P2 or .K5P3 or :3K5P;style chemicals stick;color identity;select .A:159 or .A:162 or .A:163 or .A:263 or .A:264 or .A:265 or .A:266 or .A:267 or .A:270; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 9,9'-[(2r,3r,3as,5s,7ar,9r,10r,10as,12s,14ar)-3,5,10,12-Tetrahydroxy-5,12-Dioxidooctahydro-2h,7h-Difuro[3,2-D:3',2'-J][1,3,7,9,2,8]tetraoxadiphosphacyclododecine-2,9-Diyl]bis(2-Amino-1,9-Dihydro-6h-Purin-6-One) | Ligand Info | |||||
| Structure Description | Crystal Structure of human STING bound to c-di-GMP | PDB:4EMT | ||||
| Method | X-ray diffraction | Resolution | 1.50 Å | Mutation | No | [11] |
| PDB Sequence |
SVAHGLAWSY
163 YIGYLRLILP173 ELQARIRTYN183 QHYNNLLRGA193 VSQRLYILLP203 LDCGVPDNLS 213 ADPNIRFLDK224 LPQDRVYSNS243 IYELLENGQR253 AGTCVLEYAT263 PLQTLFASQY 274 SQAGFSREDR284 LEQAKLFCRT294 LEDILADAPE304 SQNNCRLIAY314 QEPADDSSFS 324 LSQEVLRHLR334 QEE
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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 .C2E or .C2E2 or .C2E3 or :3C2E;style chemicals stick;color identity;select .A:162 or .A:163 or .A:166 or .A:167 or .A:238 or .A:239 or .A:240 or .A:260 or .A:261 or .A:263 or .A:264 or .A:267; 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: Selenomethionine | Ligand Info | |||||
| Structure Description | Crystal Structure of human STING bound to c-di-GMP | PDB:4EMT | ||||
| Method | X-ray diffraction | Resolution | 1.50 Å | Mutation | No | [11] |
| PDB Sequence |
SVAHGLAWSY
163 YIGYLRLILP173 ELQARIRTYN183 QHYNNLLRGA193 VSQRLYILLP203 LDCGVPDNLS 213 ADPNIRFLDK224 LPQDRVYSNS243 IYELLENGQR253 AGTCVLEYAT263 PLQTLFASQY 274 SQAGFSREDR284 LEQAKLFCRT294 LEDILADAPE304 SQNNCRLIAY314 QEPADDSSFS 324 LSQEVLRHLR334 QEE
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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 .MSE or .MSE2 or .MSE3 or :3MSE;style chemicals stick;color identity;select .A:155 or .A:209 or .A:210 or .A:211 or .A:212 or .A:213 or .A:215 or .A:216 or .A:266 or .A:267 or .A:268 or .A:269 or .A:270 or .A:272 or .A:273 or .A:274 or .A:277 or .A:279; 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,3R,15E,28R,29R,30R,31R,34R,36R,39S,41R)-29,41-difluoro-34,39-disulfanyl-2,33,35,38,40,42-hexaoxa-4,6,9,11,13,18,20,22,25,27-decaaza-34,39-diphosphaoctacyclo[28.6.4.1~3,36~.1~28,31~.0~4,8~.0~7,12~.0~19,24~.0~23,27~]dotetraconta-5,7,9,11,15,19,21,23,25-nonaene 34,39-dioxide (non-preferred name) | Ligand Info | |||||
| Structure Description | Crystal structure of STING in complex with E7766 | PDB:6XF3 | ||||
| Method | X-ray diffraction | Resolution | 2.38 Å | Mutation | Yes | [12] |
| PDB Sequence |
SVAHGLAWSY
163 YIGYLRLILP173 ELQARIRTYN183 QHYNNLLRGA193 VSQRLYILLP203 LDCGVPDNLS 213 MADPNIRFLD223 KLPQQTGDRA233 GIKDRVYSNS243 IYELLENGQR253 AGTCVLEYAT 263 PLQTLFAMFS280 REDRLEQAKL290 FCRTLEDILA300 DAPESQNNCR310 LIAYQEPSFS 324 LSQEVLRHLR334 QEE
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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 .V5V or .V5V2 or .V5V3 or :3V5V;style chemicals stick;color identity;select .A:162 or .A:163 or .A:166 or .A:167 or .A:232 or .A:235 or .A:238 or .A:239 or .A:240 or .A:241 or .A:263 or .A:264 or .A:267; 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 | ||||||
| References | Top | ||||
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| REF 1 | Binding-pocket and lid-region substitutions render human STING sensitive to the species-specific drug DMXAA. Cell Rep. 2014 Sep 25;8(6):1668-1676. | ||||
| REF 2 | Clathrin-associated AP-1 controls termination of STING signalling. Nature. 2022 Oct;610(7933):761-767. | ||||
| REF 3 | Identification of Novel Carbocyclic Pyrimidine Cyclic Dinucleotide STING Agonists for Antitumor Immunotherapy Using Systemic Intravenous Route. J Med Chem. 2021 May 27;64(10):6902-6923. | ||||
| REF 4 | Cyclic GMP-AMP containing mixed phosphodiester linkages is an endogenous high-affinity ligand for STING. Mol Cell. 2013 Jul 25;51(2):226-35. | ||||
| REF 5 | Molecular basis for the specific recognition of the metazoan cyclic GMP-AMP by the innate immune adaptor protein STING. Proc Natl Acad Sci U S A. 2015 Jul 21;112(29):8947-52. | ||||
| REF 6 | STING Polymer Structure Reveals Mechanisms for Activation, Hyperactivation, and Inhibition. Cell. 2019 Jul 11;178(2):290-301.e10. | ||||
| REF 7 | Enzymatic Preparation of 2'-5',3'-5'-Cyclic Dinucleotides, Their Binding Properties to Stimulator of Interferon Genes Adaptor Protein, and Structure/Activity Correlations. J Med Chem. 2019 Dec 12;62(23):10676-10690. | ||||
| REF 8 | Design of amidobenzimidazole STING receptor agonists with systemic activity. Nature. 2018 Dec;564(7736):439-443. | ||||
| REF 9 | Antitumor activity of a systemic STING-activating non-nucleotide cGAMP mimetic. Science. 2020 Aug 21;369(6506):993-999. | ||||
| REF 10 | Discovery of a Novel cGAMP Competitive Ligand of the Inactive Form of STING. ACS Med Chem Lett. 2018 Dec 6;10(1):92-97. | ||||
| REF 11 | Structure of STING bound to cyclic di-GMP reveals the mechanism of cyclic dinucleotide recognition by the immune system. Nat Struct Mol Biol. 2012 Jun 24;19(7):722-4. | ||||
| REF 12 | E7766, a Macrocycle-Bridged Stimulator of Interferon Genes (STING) Agonist with Potent Pan-Genotypic Activity. ChemMedChem. 2021 Jun 7;16(11):1740-1743. | ||||
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