Target Binding Site Detail

Content Navigation (  All   None )                                      
Target General Information
Ligand General Information
Drug Binding Sites of Target
References
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
STING_HUMAN
Ligand General Information  Top
Ligand Name Cgamp Ligand Info
Canonical SMILES C1C2C(C(C(O2)N3C=NC4=C3N=C(NC4=O)N)O)OP(=O)(OCC5C(C(C(O5)N6C=NC7=C(N=CN=C76)N)O)OP(=O)(O1)O)O
InChI 1S/C20H24N10O13P2/c21-14-8-15(24-3-23-14)29(4-25-8)18-10(31)12-6(40-18)1-38-45(36,37)43-13-7(2-39-44(34,35)42-12)41-19(11(13)32)30-5-26-9-16(30)27-20(22)28-17(9)33/h3-7,10-13,18-19,31-32H,1-2H2,(H,34,35)(H,36,37)(H2,21,23,24)(H3,22,27,28,33)/t6-,7-,10-,11-,12-,13-,18-,19-/m1/s1
InChIKey RFCBNSCSPXMEBK-INFSMZHSSA-N
PubChem Compound ID 135471108
Drug Binding Sites of Target  Top
PDB ID: 4KSY      Crystal structure of STING in complex with cGAMP
Method X-ray diffraction Resolution 1.88 Å Mutation Yes [1]
PDB Sequence
NFNVAHGLAW
161
SYYIGYLRLI
171
LPELQARIRT
181
YNQHYNNLLR
191
GAVSQRLYIL
201

LPLDCGVPDN
211
LSMADPNIRF
221
LDKLPQQTGD
231
RAGIKDRVYS
241
NSIYELLENG
251

QRAGTCVLEY
261
ATPLQTLFAM
271
SQYSQAGFSR
281
EDRLEQAKLF
291
CRTLEDILAD
301

APESQNNCRL
311
IAYQEPSFSL
325
SQEVLRHLRQ
335
E
Residue
Distance (Å)
LEU159
4.595
SER162
2.989
TYR163
3.675
GLY166
3.851
TYR167
3.487
ARG232
4.349
ILE235
4.540
ARG238
2.828
Residue
Distance (Å)
VAL239
4.363
TYR240
3.595
GLU260
3.584
TYR261
4.531
THR263
2.999
PRO264
3.257
THR267
4.893
PDB ID: 6Y99      hSTING mutant R232K in complex with 2',3'-cGAMP
Method X-ray diffraction Resolution 2.98 Å Mutation No [2]
PDB Sequence
FNVAHGLAWS
162
YYIGYLRLIL
172
PELQARIRTY
182
NQHYNAVSQR
197
LYILLPLDCG
207

VPDNLSMADP
217
NIRFLDKLPQ
227
QTGDKAGIKD
237
RVYSNSIYEL
247
LENGQRAGTC
257

VLEYATPLQT
267
LFAMSQYSQA
277
GFSREDRLEQ
287
AKLFCRTLED
297
ILADAPESQN
307

NCRLIAYQEP
317
FSLSQEVLRH
332
LRQEEKE
Residue
Distance (Å)
LEU159
4.434
SER162
2.474
TYR163
2.910
GLY166
3.010
TYR167
2.633
ALA233
4.832
ILE235
2.947
ARG238
2.216
VAL239
4.943
Residue
Distance (Å)
TYR240
3.243
SER241
3.813
GLU260
3.860
TYR261
3.855
ALA262
4.721
THR263
2.069
PRO264
2.673
THR267
2.856
PDB ID: 4LOH      Crystal structure of hSTING(H232) in complex with c[G(2',5')pA(3',5')p]
Method X-ray diffraction Resolution 2.25 Å Mutation No [3]
PDB Sequence
SVAHGLAWSY
163
YIGYLRLILP
173
ELQARIRTYN
183
QHYNNLLRGA
193
VSQRLYILLP
203

LDCGVPDNLS
213
MADPNIRFLD
223
KLPQQTGDHA
233
GIKDRVYSNS
243
IYELLENGQR
253

AGTCVLEYAT
263
PLQTLFAMSQ
273
YSQAGFSRED
283
RLEQAKLFCR
293
TLEDILADAP
303

ESQNNCRLIA
313
YQEPADDSSF
323
SLSQEVLRHL
333
RQEE
Residue
Distance (Å)
SER162
3.322
TYR163
3.355
GLY166
4.026
TYR167
3.361
ILE235
3.774
ARG238
2.995
VAL239
3.858
Residue
Distance (Å)
TYR240
3.542
SER241
4.726
GLU260
4.424
THR263
3.130
PRO264
3.223
THR267
4.073
PDB ID: 6DNK      Human Stimulator of Interferon Genes
Method X-ray diffraction Resolution 1.95 Å Mutation No [4]
PDB Sequence
NVAHGLAWSY
163
YIGYLRLILP
173
ELQARIRTYN
183
QHYAVSQRLY
199
ILLPLDCGVP
209

DNLSMADPNI
219
RFLDKLPQQT
229
ADRAGIKDRV
239
YSNSIYELLE
249
NGQRAGTCVL
259

EYATPLQTLF
269
AMSQYSQAGF
279
SREDRLEQAK
289
LFCRTLEDIL
299
ADAPESQNNC
309

RLIAYQEPAS
322
FSLSQEVLRH
332
LRQ
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:238 or .A:239 or .A:240 or .A:241 or .A:260 or .A:261 or .A:263 or .A:264; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
LEU159
4.559
SER162
2.984
TYR163
3.353
GLY166
3.365
TYR167
3.058
ARG232
3.632
ARG238
2.559
Residue
Distance (Å)
VAL239
3.264
TYR240
3.264
SER241
4.451
GLU260
3.880
TYR261
4.716
THR263
1.833
PRO264
3.388
References  Top
REF 1 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 2 Ligand Strain and Its Conformational Complexity Is a Major Factor in the Binding of Cyclic Dinucleotides to STING Protein. Angew Chem Int Ed Engl. 2021 Apr 26;60(18):10172-10178.
REF 3 Structure-function analysis of STING activation by c[G(2',5')pA(3',5')p] and targeting by antiviral DMXAA. Cell. 2013 Aug 15;154(4):748-62.
REF 4 STING Polymer Structure Reveals Mechanisms for Activation, Hyperactivation, and Inhibition. Cell. 2019 Jul 11;178(2):290-301.e10.

If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.