Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T58921 | Target Info | |||
| Target Name | Peroxisome proliferator-activated receptor gamma (PPAR-gamma) | ||||
| Synonyms | PPAR-gamma; Nuclear receptor subfamily 1 group C member 3; NR1C3 | ||||
| Target Type | Successful Target | ||||
| Gene Name | PPARG | ||||
| Biochemical Class | Nuclear hormone receptor | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | GW1929 | Ligand Info | |||
| Canonical SMILES | CN(CCOC1=CC=C(C=C1)CC(C(=O)O)NC2=CC=CC=C2C(=O)C3=CC=CC=C3)C4=CC=CC=N4 | ||||
| InChI | 1S/C30H29N3O4/c1-33(28-13-7-8-18-31-28)19-20-37-24-16-14-22(15-17-24)21-27(30(35)36)32-26-12-6-5-11-25(26)29(34)23-9-3-2-4-10-23/h2-18,27,32H,19-21H2,1H3,(H,35,36)/t27-/m0/s1 | ||||
| InChIKey | QTQMRBZOBKYXCG-MHZLTWQESA-N | ||||
| PubChem Compound ID | 6518171 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 6D8X PPAR gamma LBD complexed with the agonist GW1929 | ||||||
| Method | X-ray diffraction | Resolution | 1.90 Å | Mutation | No | [1] |
| PDB Sequence |
GQLNPESADL
211 RALAKHLYDS221 YIKSFPLTKA231 KARAILTGKT241 TDKSPFVIYD251 MNSLMMGEDK 261 IKFKHITPLQ271 EQSKEVAIRI281 FQGCQFRSVE291 AVQEITEYAK301 SIPGFVNLDL 311 NDQVTLLKYG321 VHEIIYTMLA331 SLMNKDGVLI341 SEGQGFMTRE351 FLKSLRKPFG 361 DFMEPKFEFA371 VKFNALELDD381 SDLAIFIAVI391 ILSGDRPGLL401 NVKPIEDIQD 411 NLLQALELQL421 KLNHPESSQL431 FAKLLQKMTD441 LRQIVTEHVQ451 LLQVIKKTET 461 DMSLHPLLQE471 IYKDLY
|
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|
|
ILE262
4.241
ILE281
3.896
PHE282
3.334
GLY284
3.671
CYS285
3.424
GLN286
3.708
ARG288
4.135
SER289
2.562
HIS323
2.715
ILE326
3.898
TYR327
3.663
LEU330
3.626
VAL339
4.037
LEU340
4.708
|
|||||
| PDB ID: 6D94 Crystal structure of PPAR gamma in complex with Mediator of RNA polymerase II transcription subunit 1 | ||||||
| Method | X-ray diffraction | Resolution | 1.90 Å | Mutation | No | [2] |
| PDB Sequence |
ESADLRALAK
216 HLYDSYIKSF226 PLTKAKARAI236 LTGKTTDKSP246 FVIYDMNSLM256 MGEDKIKFKH 266 ITPLQEQSKE276 VAIRIFQGCQ286 FRSVEAVQEI296 TEYAKSIPGF306 VNLDLNDQVT 316 LLKYGVHEII326 YTMLASLMNK336 DGVLISEGQG346 FMTREFLKSL356 RKPFGDFMEP 366 KFEFAVKFNA376 LELDDSDLAI386 FIAVIILSGD396 RPGLLNVKPI406 EDIQDNLLQA 416 LELQLKLNHP426 ESSQLFAKLL436 QKMTDLRQIV446 TEHVQLLQVI456 KKTETDMSLH 466 PLLQEIYKDL476 Y
|
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|
|
ILE262
3.854
ILE281
3.777
PHE282
3.315
GLY284
3.461
CYS285
3.244
GLN286
3.359
ARG288
4.106
SER289
2.745
HIS323
2.630
ILE326
3.864
TYR327
3.961
LEU330
3.668
VAL339
3.821
|
|||||
| PDB ID: 6T1S PPAR mutant | ||||||
| Method | X-ray diffraction | Resolution | 1.65 Å | Mutation | Yes | [3] |
| PDB Sequence |
MQLNPESADL
239 RALAKHLYDS249 YIKSFPLTKA259 KARAILTTTD271 KSPFVIYDMN281 SLMMGEDKIK 291 FKHITPLQEQ301 SKEVAIRISQ311 GCQFRSVEAV321 QEITEYAKSI331 PGFVNLDLND 341 QVTLLKYGVH351 EIIYTMLASL361 MNKDGVLISE371 GQGFMTREFL381 KSLRKPFGDF 391 MEPKFEFAVK401 FNALELDDSD411 LAIFIAVIIL421 SGDRPGLLNV431 KPIEDIQDNL 441 LQALELQLKL451 NHPESSQLFA461 KLLQKMTDLR471 QIVTEHVQLL481 QVIKKTETDM 491 SLHPLLQEIY501 KDLY
|
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|
ILE290
2.431
LYS291
4.352
ALA306
4.430
ARG308
4.879
ILE309
2.545
SER310
2.403
GLN311
4.910
GLY312
2.536
CYS313
2.384
GLN314
2.688
ARG316
2.689
SER317
1.813
HIS351
2.206
ILE354
3.195
TYR355
2.064
LEU358
2.504
MET362
4.533
VAL367
2.758
LEU368
3.743
|
|||||
| PDB ID: 6FZF PPAR mutant complex | ||||||
| Method | X-ray diffraction | Resolution | 1.95 Å | Mutation | Yes | [4] |
| PDB Sequence |
ESADLRALAK
244 HLYDSYIKSF254 PLTKAKARAI264 LTGKTTDKSP274 FVIYDMNSLM284 MGEDKIKFKH 294 ITPLQEQSKE304 VAIRIFQGCQ314 FRSVEAVQEI324 TEYAKSIPGF334 VNLDLNDQVT 344 LLKYGVHEII354 YTMLASLMNK364 DGVLISEGQG374 FMTREFLKSL384 RKPFGDFMEP 394 KFEFAVKFNA404 LELDDSDLAI414 FIAVIILSGD424 RPGLLNVKPI434 EDIQDNLLQA 444 LELQLKLNHP454 ESSQLFAKLL464 QKMTDLRQIV474 MEHVQLLQVI484 KKTETDMSLH 494 PLLQEIYKDL504 Y
|
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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 .EDK or .EDK2 or .EDK3 or :3EDK;style chemicals stick;color identity;select .A:290 or .A:309 or .A:310 or .A:312 or .A:313 or .A:314 or .A:316 or .A:317 or .A:351 or .A:354 or .A:355 or .A:358 or .A:367 or .A:368 or .A:369 or .A:376 or .A:381 or .A:384 or .A:388 or .A:391 or .A:392 or .A:477 or .A:481 or .A:493 or .A:497 or .A:501; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
ILE290
3.981
ILE309
3.719
PHE310
3.264
GLY312
3.373
CYS313
3.238
GLN314
3.398
ARG316
3.955
SER317
2.732
HIS351
2.690
ILE354
3.769
TYR355
3.660
LEU358
3.643
VAL367
4.248
|
|||||
| PDB ID: 6T1V Structure of PPARg H494Y mutant in complex with GW1929 | ||||||
| Method | X-ray diffraction | Resolution | 2.21 Å | Mutation | Yes | [5] |
| PDB Sequence |
DLRALAKHLY
247 DSYIKSFPLT257 KAKARAILTG267 KTTDKSPFVI277 YDMNSLMMGE287 DKIKFKHITP 297 LQEQSKEVAI307 RIFQGCQFRS317 VEAVQEITEY327 AKSIPGFVNL337 DLNDQVTLLK 347 YGVHEIIYTM357 LASLMNKDGV367 LISEGQGFMT377 REFLKSLRKP387 FGDFMEPKFE 397 FAVKFNALEL407 DDSDLAIFIA417 VIILSGDRPG427 LLNVKPIEDI437 QDNLLQALEL 447 QLKLNHPESS457 QLFAKLLQKM467 TDLRQIVTEH477 VQLLQVIKKT487 ETDMSLYPLL 497 QEIYKDLY
|
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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 .EDK or .EDK2 or .EDK3 or :3EDK;style chemicals stick;color identity;select .A:290 or .A:309 or .A:310 or .A:312 or .A:313 or .A:314 or .A:316 or .A:317 or .A:351 or .A:354 or .A:355 or .A:358 or .A:367 or .A:368 or .A:369 or .A:376 or .A:381 or .A:384 or .A:388 or .A:391 or .A:392 or .A:477 or .A:481 or .A:493 or .A:497 or .A:501; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
ILE290
4.077
ILE309
3.736
PHE310
3.281
GLY312
3.477
CYS313
3.369
GLN314
3.302
ARG316
4.091
SER317
2.814
HIS351
2.622
ILE354
3.893
TYR355
3.986
LEU358
3.622
VAL367
4.230
|
|||||
| PDB ID: 6FZG PPAR gamma mutant complex | ||||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | Yes | [4] |
| PDB Sequence |
MQLNPESADL
239 RALAKHLYDS249 YIKSFPLTKA259 KARAILTGKT269 TDKSPFVIYD279 MNSLMMGEDK 289 MKFKHITPLQ299 EQSKEVAIRI309 FQGCQFRSVE319 AVQEITEYAK329 SIPGFVNLDL 339 NDQVTLLKYG349 VHEIIYTMLA359 SLMNKDGVLI369 SEGQGFMTRE379 FLKSLRKPFG 389 DFMEPKFEFA399 VKFNALELDD409 SDLAIFIAVI419 ILSGDRPGLL429 NVKPIEDIQD 439 NLLQALELQL449 KLNHPESSQL459 FAKLLQKMTD469 LRQIVTEHVQ479 LLQVIKKTET 489 DMSLHPLLQE499 IYKDLY
|
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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 .EDK or .EDK2 or .EDK3 or :3EDK;style chemicals stick;color identity;select .A:292 or .A:309 or .A:310 or .A:312 or .A:313 or .A:314 or .A:316 or .A:317 or .A:351 or .A:354 or .A:355 or .A:358 or .A:367 or .A:368 or .A:369 or .A:376 or .A:381 or .A:388 or .A:391 or .A:392 or .A:395 or .A:477 or .A:481 or .A:484 or .A:493 or .A:497 or .A:501; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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PHE292
3.824
ILE309
3.834
PHE310
3.472
GLY312
3.626
CYS313
3.468
GLN314
3.594
ARG316
4.185
SER317
2.607
HIS351
2.769
ILE354
4.155
TYR355
3.781
LEU358
3.908
VAL367
3.708
LEU368
4.774
|
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| PDB ID: 7JQG Crystal structure of human PPARgamma ligand binding domain Y473E mutant in complex with GW1929 | ||||||
| Method | X-ray diffraction | Resolution | 2.15 Å | Mutation | Yes | [6] |
| PDB Sequence |
ESADLRALAK
216 HLYDSYIKSF226 PLTKAKARAI236 LTTDKSPFVI249 YDMNSLMMGE259 KEVAIRIFQG 284 CQFRSVEAVQ294 EITEYAKSIP304 GFVNLDLNDQ314 VTLLKYGVHE324 IIYTMLASLM 334 NKDGVLISEG344 QGFMTREFLK354 SLRKPFGDFM364 EPKFEFAVKF374 NALELDDSDL 384 AIFIAVIILS394 GDRPGLLNVK404 PIEDIQDNLL414 QALELQLKLN424 HPESSQLFAK 434 LLQKMTDLRQ444 IVTEHVQLLQ454 VIKKTETDMS464 LHPLLQEIEK474 |
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .EDK or .EDK2 or .EDK3 or :3EDK;style chemicals stick;color identity;select .A:280 or .A:281 or .A:283 or .A:284 or .A:285 or .A:287 or .A:288 or .A:289 or .A:292 or .A:326 or .A:330 or .A:333 or .A:339 or .A:340 or .A:341 or .A:342 or .A:343 or .A:348 or .A:353 or .A:364; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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ARG280
4.756
ILE281
4.313
GLN283
4.539
GLY284
2.802
CYS285
2.431
PHE287
3.394
ARG288
2.821
SER289
3.102
ALA292
4.630
ILE326
4.212
|
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| PDB ID: 7RLE Crystal structure of PPAR gamma in complex with CREB-binding protein and agonist GW1929 | ||||||
| Method | X-ray diffraction | Resolution | 2.50 Å | Mutation | No | [2] |
| PDB Sequence |
ESADLRALAK
216 HLYDSYIKSF226 PLTKAKARAI236 LTGKTTDKSP246 FVIYDMNSLM256 MGEDKIKFKH 266 EVAIRIFQGC285 QFRSVEAVQE295 ITEYAKSIPG305 FVNLDLNDQV315 TLLKYGVHEI 325 IYTMLASLMN335 KDGVLISEGQ345 GFMTREFLKS355 LRKPFGDFME365 PKFEFAVKFN 375 ALELDDSDLA385 IFIAVIILSG395 DRPGLLNVKP405 IEDIQDNLLQ415 ALELQLKLNH 425 PESSQLFAKL435 LQKMTDLRQI445 VTEHVQLLQV455 IKKTETDMSL465 HPLLQEIYKD 475 LY
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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 .EDK or .EDK2 or .EDK3 or :3EDK;style chemicals stick;color identity;select .A:281 or .A:282 or .A:284 or .A:285 or .A:286 or .A:288 or .A:289 or .A:323 or .A:326 or .A:327 or .A:330 or .A:339 or .A:340 or .A:341 or .A:348 or .A:356 or .A:360 or .A:363 or .A:364 or .A:367 or .A:449 or .A:453 or .A:456 or .A:465 or .A:469 or .A:473; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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ILE281
3.884
PHE282
3.366
GLY284
3.594
CYS285
3.538
GLN286
3.545
ARG288
4.094
SER289
3.000
HIS323
2.642
ILE326
3.878
TYR327
3.981
LEU330
3.772
VAL339
3.950
LEU340
4.509
|
|||||
| PDB ID: 6FZJ PPAR gamma mutant complex | ||||||
| Method | X-ray diffraction | Resolution | 2.01 Å | Mutation | Yes | [4] |
| PDB Sequence |
ADLRALAKHL
246 YDSYIKSFPL256 TKAKARAILT266 GKTTDKSPFV276 IYDINSLMMG286 EDKIKFKHIT 296 PEQSKEVAIR308 IFQGCQFRSV318 EAVQEITEYA328 KSIPGFVNLD338 LNDQVTLLKY 348 GVHEIIYTML358 ASLMNKDGVL368 ISEGQGFMTR378 EFLKSLRKPF388 GDFMEPKFEF 398 AVKFNALELD408 DSDLAIFIAV418 IILSGDRPGL428 LNVKPIEDIQ438 DNLLQALELQ 448 LKLNHPESSQ458 LFAKLLQKMT468 DLRQIVTEHV478 QLLQVIKKTE488 TDMSLHPLLQ 498 EIYKDLY
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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 .EDK or .EDK2 or .EDK3 or :3EDK;style chemicals stick;color identity;select .A:292 or .A:309 or .A:310 or .A:312 or .A:313 or .A:314 or .A:316 or .A:317 or .A:351 or .A:354 or .A:355 or .A:358 or .A:367 or .A:368 or .A:369 or .A:376 or .A:381 or .A:384 or .A:388 or .A:391 or .A:392 or .A:395 or .A:477 or .A:481 or .A:493 or .A:497 or .A:501; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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PHE292
3.885
ILE309
3.902
PHE310
3.292
GLY312
3.622
CYS313
3.244
GLN314
3.527
ARG316
4.011
SER317
2.841
HIS351
2.552
ILE354
3.874
TYR355
3.879
LEU358
3.714
VAL367
4.222
LEU368
4.770
|
|||||
| PDB ID: 6VZL Crystal structure of human PPARgamma ligand binding domain in complex with GW1929 | ||||||
| Method | X-ray diffraction | Resolution | 2.07 Å | Mutation | No | [6] |
| PDB Sequence |
ESADLRALAK
216 HLYDSYIKSF226 PLTKAKARAI236 LTGTDKSPFV248 IYDMNSLMMG258 EDKIEVAIRI 281 FQGCQFRSVE291 AVQEITEYAK301 SIPGFVNLDL311 NDQVTLLKYG321 VHEIIYTMLA 331 SLMNKDGVLI341 SEGQGFMTRE351 FLKSLRKPFG361 DFMEPKFEFA371 VKFNALELDD 381 SDLAIFIAVI391 ILSGDRPGLL401 NVKPIEDIQD411 NLLQALELQL421 KLNHPESSQL 431 FAKLLQKMTD441 LRQIVTEHVQ451 LLQVIKKTET461 DMSLHPLLQE471 IYK |
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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 .EDK or .EDK2 or .EDK3 or :3EDK;style chemicals stick;color identity;select .A:281 or .A:282 or .A:284 or .A:285 or .A:286 or .A:288 or .A:289 or .A:323 or .A:326 or .A:327 or .A:330 or .A:333 or .A:339 or .A:340 or .A:341 or .A:342 or .A:353 or .A:356 or .A:360 or .A:363 or .A:364 or .A:367 or .A:449 or .A:453 or .A:465 or .A:469 or .A:473; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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ILE281
4.041
PHE282
3.210
GLY284
3.719
CYS285
3.174
GLN286
3.346
ARG288
3.515
SER289
2.862
HIS323
2.910
ILE326
3.906
TYR327
3.679
LEU330
3.644
LEU333
3.624
VAL339
4.588
LEU340
3.719
|
|||||
| PDB ID: 6FZP PPAR gamma complex. | ||||||
| Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | No | [4] |
| PDB Sequence |
ESADLRALAK
244 HLYDSYIKSF254 PLTKAKARAI264 LTGKTTSPFV276 IYDMNSLMMG286 EDKIKFEVAI 307 RIFQGCQFRS317 VEAVQEITEY327 AKSIPGFVNL337 DLNDQVTLLK347 YGVHEIIYTM 357 LASLMNKDGV367 LISEGQGFMT377 REFLKSLRKP387 FGDFMEPKFE397 FAVKFNALEL 407 DDSDLAIFIA417 VIILSGDRPG427 LLNVKPIEDI437 QDNLLQALEL447 QLKLNHPESS 457 QLFAKLLQKM467 TDLRQIVTEH477 VQLLQVIKKT487 ETDMSLHPLL497 QEIYKDLY |
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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 .EDK or .EDK2 or .EDK3 or :3EDK;style chemicals stick;color identity;select .A:290 or .A:309 or .A:310 or .A:312 or .A:313 or .A:314 or .A:316 or .A:317 or .A:351 or .A:354 or .A:355 or .A:358 or .A:367 or .A:368 or .A:369 or .A:376 or .A:381 or .A:384 or .A:388 or .A:391 or .A:392 or .A:395 or .A:477 or .A:481 or .A:493 or .A:497 or .A:501; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
ILE290
4.474
ILE309
3.478
PHE310
3.388
GLY312
3.502
CYS313
3.372
GLN314
3.503
ARG316
4.390
SER317
2.704
HIS351
2.634
ILE354
4.267
TYR355
4.018
LEU358
3.767
VAL367
4.177
LEU368
4.617
|
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | PPAR gamma LBD complexed with the agonist GW1929 | ||||
| REF 2 | A structural mechanism of nuclear receptor biased agonism. Proc Natl Acad Sci U S A. 2022 Dec 13;119(50):e2215333119. | ||||
| REF 3 | Structure of PPARg mutant | ||||
| REF 4 | Recurrent activating mutations of PPARGamma associated with luminal bladder tumors. Nat Commun. 2019 Jan 16;10(1):253. | ||||
| REF 5 | Structure of a PPARg mutant complex | ||||
| REF 6 | Structural mechanism underlying ligand binding and activation of PPARGamma. Structure. 2021 Sep 2;29(9):940-950.e4. | ||||
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