Target Binding Site Detail
| 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 | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | Alpha-Aminoisobutyric Acid | Ligand Info | |||
| Canonical SMILES | CC(C)(C(=O)O)N | ||||
| InChI | 1S/C4H9NO2/c1-4(2,5)3(6)7/h5H2,1-2H3,(H,6,7) | ||||
| InChIKey | FUOOLUPWFVMBKG-UHFFFAOYSA-N | ||||
| PubChem Compound ID | 6119 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 7RBT cryo-EM structure of human Gastric inhibitory polypeptide receptor GIPR bound to tirzepatide | ||||||
| Method | Electron microscopy | Resolution | 3.08 Å | Mutation | No | [1] |
| PDB Sequence |
GQTAGELYQR
38 WERYRRECQE48 TLAAAEPPSG58 LACNGSFDMY68 VCWDYAAPNA78 TARASCPWYL 88 PWHHHVAAGF98 VLRQCGSDGQ108 WGLWRDHTQC118 ENPEKNEAFL128 DQRLILERLQ 138 VMYTVGYSLS148 LATLLLALLI158 LSLFRRLHCT168 RNYIHINLFT178 SFMLRAAAIL 188 SRDRLLPRPG198 PYLGDQALAL208 WNQALAACRT218 AQIVTQYCVG228 ANYTWLLVEG 238 VYLHSLLVLV248 GGSEEGHFRY258 YLLLGWGAPA268 LFVIPWVIVR278 YLYENTQCWE 288 RNEVKAIWWI298 IRTPILMTIL308 INFLIFIRIL318 GILLSKLRTR328 DYRLRLARST 343 LTLVPLLGVH353 EVVFAPVTEE363 QARGALRFAK373 LGFEIFLSSF383 QGFLVSVLYC 393 FINKEVQSEI403 RRGWHHCR
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| 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 ERYRRECQET49 LAAAACNGSF65 DMYVCWDYAA75 PNATARASCP85 WYLPWHHHVA 95 AGFVLRQCGS105 DGQWGLWRDH115 TQCENPEKNE125 AFLDQRLILE135 RLQVMYTVGY 145 SLSLATLLLA155 LLILSLFRRL165 HCTRNYIHIN175 LFTSFMLRAA185 AILSRDRLLP 195 RPGPYLGDQA205 LALWNQALAA215 CRTAQIVTQY225 CVGANYTWLL235 VEGVYLHSLL 245 VLVGGSEEGH255 FRYYLLLGWG265 APALFVIPWV275 IVRYLYENTQ285 CWERNEVKAI 295 WWIIRTPILM305 TILINFLIFI315 RILGILLSKL325 RTRQMRCRDY335 RLRLARSTLF 345 LVPLLGVHEV355 VFAPVTEEQA365 RGALRFAKLG375 FEIFLSSFQG385 FLVSVLYCFI 395 NKEVQSEIRR405 GWHHCRLRRS415
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| 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 ERYRRECQEF127 LDQRLILERL137 QVMYTVGYSL147 SLATLLLALL157 ILSLFRRLHC 167 TRNYIHINLF177 TSFMLRAAAI187 LSRDRLLPRP197 LWNQALAACR217 TAQIVTQYCV 227 GANYTWLLVE237 GVYLHSLLVL247 VGGSEEGHFR257 YYLLLGWGAP267 ALFVIPWVIV 277 RYLYENTQCW287 ERNEVKAIWW297 IIRTPILMTI307 LINFLIFIRI317 LGILLSKLRT 327 RQDYRLRLAR341 STLFLVPLLG351 VHEVVFAPVE363 QARGALRFAK373 LGFEIFLSSF 383 QGFLVSVLYC393 FINKEVQSEI403 RRGWHHCR
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| 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 ERYRRECQET49 ACNGSFDMYV69 CWDYAAPNAT79 ARASCPWYLP89 WHHHVAAGFV 99 LRQCGWRDHT116 QCENPEKNEA126 FLDQRLILER136 LQVMYTVGYS146 LSLATLLLAL 156 LILSLFRRLH166 CTRNYIHINL176 FTSFMLRAAA186 ILSRDRLLPR196 PGPYLLWNQA 212 LAACRTAQIV222 TQYCVGANYT232 WLLVEGVYLH242 SLLVLVGGSE252 EGHFRYYLLL 262 GWGAPALFVI272 PWVIVRYLYE282 NTQCWERNEV292 KAIWWIIRTP302 ILMTILINFL 312 IFIRILGILL322 SKLRTRCRDY335 RLRLARSTLF345 LVPLLGVHEV355 VFAPVTEEQA 365 RGALRFAKLG375 FEIFLSSFQG385 FLVSVLYCFI395 NKEVQSEIRR405 GWHHCRLRR |
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Click to Show 3D Structure of This Binding Site
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Structural determinants of dual incretin receptor agonism by tirzepatide. Proc Natl Acad Sci U S A. 2022 Mar 29;119(13):e2116506119. | ||||
| 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. | ||||
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