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 T41750 Target Info
Target Name Gastric inhibitory polypeptide receptor (GIPR)
Synonyms Glucosedependent insulinotropic polypeptide receptor; GIPR
Target Type Successful Target
Gene Name GIPR
Biochemical Class GPCR secretin
UniProt ID
GIPR_HUMAN
Ligand General Information  Top
Ligand Name Cholesterol Ligand Info
Canonical SMILES CC(C)CCCC(C)C1CCC2C1(CCC3C2CC=C4C3(CCC(C4)O)C)C
InChI 1S/C27H46O/c1-18(2)7-6-8-19(3)23-11-12-24-22-10-9-20-17-21(28)13-15-26(20,4)25(22)14-16-27(23,24)5/h9,18-19,21-25,28H,6-8,10-17H2,1-5H3/t19-,21+,22+,23-,24+,25+,26+,27-/m1/s1
InChIKey HVYWMOMLDIMFJA-DPAQBDIFSA-N
PubChem Compound ID 5997
Drug Binding Sites of Target  Top
PDB ID: 7DTY      Structural basis of ligand selectivity conferred by the human glucose-dependent insulinotropic polypeptide receptor
Method Electron microscopy Resolution 2.98 Å Mutation No [1]
PDB Sequence
TAGELYQRWE
40
RYRRECQETA
60
CNGSFDMYVC
70
WDYAAPNATA
80
RASCPWYLPW
90

HHHVAAGFVL
100
RQCWRDHTQC
118
ENPEKNEAFL
128
DQRLILERLQ
138
VMYTVGYSLS
148

LATLLLALLI
158
LSLFRRLHCT
168
RNYIHINLFT
178
SFMLRAAAIL
188
SRDRLLPRPG
198

PYLGDQALAL
208
WNQALAACRT
218
AQIVTQYCVG
228
ANYTWLLVEG
238
VYLHSLLVLV
248

GGSEEGHFRY
258
YLLLGWGAPA
268
LFVIPWVIVR
278
YLYENTQCWE
288
RNEVKAIWWI
298

IRTPILMTIL
308
INFLIFIRIL
318
GILLSKLRTR
328
QMRCRDYRLR
338
LARSTLFLVP
348

LLGVHEVVFA
358
PVTEEQARGA
368
LRFAKLGFEI
378
FLSSFQGFLV
388
SVLYCFINKE
398

VQSEIRRGWH
408
HCRLRRS
Residue
Distance (Å)
ILE133
3.730
LEU137
4.531
MET140
3.635
TYR171
4.471
ILE174
4.340
ASN175
3.540
THR178
3.749
LEU182
4.364
ALA214
4.943
ARG217
3.733
THR218
3.616
ILE221
4.154
TYR225
3.638
LEU235
4.415
VAL239
4.105
HIS242
3.834
LEU247
4.606
LEU260
3.712
LEU262
4.346
TRP264
3.417
ALA266
3.729
LEU269
4.619
PHE270
4.803
Residue
Distance (Å)
PRO273
4.752
TYR279
4.265
ALA294
4.451
TRP297
3.508
ILE298
3.756
THR301
3.693
MET305
3.765
ILE309
4.014
PHE311
4.955
ILE313
4.837
PHE314
4.027
ILE315
4.796
LEU318
3.753
LEU322
3.709
THR343
4.947
VAL356
3.809
ALA368
3.527
PHE371
3.678
ALA372
3.508
GLY375
3.806
PHE376
4.791
PHE379
3.585
PDB ID: 7FIN      Cryo-EM structure of the GIPR/GLP-1R/GCGR triagonist peptide 20-bound human GIPR-Gs complex
Method Electron microscopy Resolution 3.10 Å Mutation Yes [2]
PDB Sequence
QTAGELYQRW
39
ERYRRECQET
49
LAAAACNGSF
65
DMYVCWDYAA
75
PNATARASCP
85

WYLPWHHHVA
95
AGFVLRQCGS
105
DGQWGLWRDH
115
TQCENPEKNE
125
AFLDQRLILE
135

RLQVMYTVGY
145
SLSLATLLLA
155
LLILSLFRRL
165
HCTRNYIHIN
175
LFTSFMLRAA
185

AILSRDRLLP
195
RPGPYLGDQA
205
LALWNQALAA
215
CRTAQIVTQY
225
CVGANYTWLL
235

VEGVYLHSLL
245
VLVGGSEEGH
255
FRYYLLLGWG
265
APALFVIPWV
275
IVRYLYENTQ
285

CWERNEVKAI
295
WWIIRTPILM
305
TILINFLIFI
315
RILGILLSKL
325
RTRQMRCRDY
335

RLRLARSTLF
345
LVPLLGVHEV
355
VFAPVTEEQA
365
RGALRFAKLG
375
FEIFLSSFQG
385

FLVSVLYCFI
395
NKEVQSEIRR
405
GWHHCRLRRS
415
Residue
Distance (Å)
GLU135
4.840
ARG136
3.739
VAL139
3.972
MET140
4.088
LEU147
4.657
TYR171
4.415
ILE174
4.501
ASN175
3.407
THR178
4.099
LEU182
4.185
ALA214
4.918
ARG217
3.821
THR218
3.302
ILE221
3.895
VAL222
4.521
TYR225
3.663
LEU235
3.893
VAL239
3.814
HIS242
3.482
VAL246
4.527
LEU247
4.577
LEU260
3.881
LEU262
3.854
TRP264
3.424
ALA266
3.890
LEU269
4.801
PHE270
4.913
VAL275
4.493
TYR279
3.506
Residue
Distance (Å)
ASN283
4.921
TRP287
4.468
ALA294
3.768
TRP297
3.496
ILE298
3.789
THR301
3.534
MET305
4.117
ILE309
4.264
PHE311
4.602
PHE314
4.816
ILE315
4.559
ARG316
4.549
LEU318
3.700
GLY319
4.559
LEU322
3.687
LEU339
4.724
ARG341
3.527
THR343
3.765
LEU344
4.289
VAL347
4.167
VAL352
3.755
VAL356
4.774
PHE379
4.472
PHE383
4.034
LEU387
4.135
VAL390
4.764
LEU391
3.942
ILE395
3.754
PDB ID: 7VAB      Cryo-EM structure of the non-acylated tirzepatide (LY3298176)-bound human GIPR-Gs complex
Method Electron microscopy Resolution 3.20 Å Mutation Yes [2]
PDB Sequence
QTAGELYQRW
39
ERYRRECQEF
127
LDQRLILERL
137
QVMYTVGYSL
147
SLATLLLALL
157

ILSLFRRLHC
167
TRNYIHINLF
177
TSFMLRAAAI
187
LSRDRLLPRP
197
LWNQALAACR
217

TAQIVTQYCV
227
GANYTWLLVE
237
GVYLHSLLVL
247
VGGSEEGHFR
257
YYLLLGWGAP
267

ALFVIPWVIV
277
RYLYENTQCW
287
ERNEVKAIWW
297
IIRTPILMTI
307
LINFLIFIRI
317

LGILLSKLRT
327
RQDYRLRLAR
341
STLFLVPLLG
351
VHEVVFAPVE
363
QARGALRFAK
373

LGFEIFLSSF
383
QGFLVSVLYC
393
FINKEVQSEI
403
RRGWHHCR
Residue
Distance (Å)
ILE133
3.751
TYR171
3.894
ILE174
4.092
ASN175
3.505
THR178
3.784
LEU182
4.620
ALA214
4.787
ARG217
3.063
THR218
3.911
ILE221
3.763
TYR225
3.655
LEU260
3.729
TRP264
3.461
PRO273
3.787
ILE276
3.739
VAL277
4.768
TYR279
3.653
LEU280
3.808
TYR281
3.400
TRP287
4.368
Residue
Distance (Å)
ALA294
3.750
ILE295
4.719
ILE298
3.777
THR301
3.789
MET305
4.079
PHE311
4.807
PHE314
3.768
LEU318
3.742
LEU322
4.283
THR343
4.066
VAL347
4.161
VAL352
4.737
HIS353
4.203
VAL356
4.723
ALA368
4.770
PHE371
3.800
ALA372
4.268
GLY375
3.712
PHE376
4.732
PHE379
3.636
PDB ID: 7FIY      Cryo-EM structure of the tirzepatide-bound human GIPR-Gs complex
Method Electron microscopy Resolution 3.40 Å Mutation Yes [2]
PDB Sequence
QTAGELYQRW
39
ERYRRECQET
49
ACNGSFDMYV
69
CWDYAAPNAT
79
ARASCPWYLP
89

WHHHVAAGFV
99
LRQCGWRDHT
116
QCENPEKNEA
126
FLDQRLILER
136
LQVMYTVGYS
146

LSLATLLLAL
156
LILSLFRRLH
166
CTRNYIHINL
176
FTSFMLRAAA
186
ILSRDRLLPR
196

PGPYLLWNQA
212
LAACRTAQIV
222
TQYCVGANYT
232
WLLVEGVYLH
242
SLLVLVGGSE
252

EGHFRYYLLL
262
GWGAPALFVI
272
PWVIVRYLYE
282
NTQCWERNEV
292
KAIWWIIRTP
302

ILMTILINFL
312
IFIRILGILL
322
SKLRTRCRDY
335
RLRLARSTLF
345
LVPLLGVHEV
355

VFAPVTEEQA
365
RGALRFAKLG
375
FEIFLSSFQG
385
FLVSVLYCFI
395
NKEVQSEIRR
405

GWHHCRLRR
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .CLR or .CLR2 or .CLR3 or :3CLR;style chemicals stick;color identity;select .R:133 or .R:174 or .R:175 or .R:178 or .R:182 or .R:217 or .R:218 or .R:221 or .R:222 or .R:225 or .R:235 or .R:239 or .R:242 or .R:247 or .R:260 or .R:262 or .R:264 or .R:266 or .R:270 or .R:273 or .R:275 or .R:277 or .R:281 or .R:294 or .R:306 or .R:309 or .R:322 or .R:339 or .R:340 or .R:343 or .R:344 or .R:368 or .R:371 or .R:372 or .R:375 or .R:379; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ILE133
3.965
ILE174
4.692
ASN175
3.291
THR178
4.087
LEU182
4.493
ARG217
3.949
THR218
4.340
ILE221
3.724
VAL222
4.732
TYR225
3.645
LEU235
4.154
VAL239
3.903
HIS242
3.465
LEU247
4.396
LEU260
3.883
LEU262
4.336
TRP264
3.470
ALA266
3.916
Residue
Distance (Å)
PHE270
3.688
PRO273
4.220
VAL275
4.609
VAL277
3.825
TYR281
4.875
ALA294
4.355
THR306
4.767
ILE309
4.118
LEU322
4.052
LEU339
3.730
ALA340
4.696
THR343
3.731
LEU344
3.786
ALA368
4.528
PHE371
3.793
ALA372
3.755
GLY375
4.193
PHE379
3.644
References  Top
REF 1 Structural insights into hormone recognition by the human glucose-dependent insulinotropic polypeptide receptor. Elife. 2021 Jul 13;10:e68719.
REF 2 Structural insights into multiplexed pharmacological actions of tirzepatide and peptide 20 at the GIP, GLP-1 or glucagon receptors. Nat Commun. 2022 Feb 25;13(1):1057.

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