Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T25307 | Target Info | |||
| Target Name | Nuclear receptor ROR-gamma (RORG) | ||||
| Synonyms | Retinoid-related orphan receptor-gamma; RZRG; RORG; RAR-related orphan receptor C; Nuclear receptor subfamily 1 group F member 3; Nuclear receptor RZR-gamma; NR1F3 | ||||
| Target Type | Clinical trial Target | ||||
| Gene Name | RORC | ||||
| Biochemical Class | Nuclear hormone receptor | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | 4-{1-[2-Chloro-6-(Trifluoromethyl)benzoyl]-1h-Indazol-3-Yl}benzoic Acid | Ligand Info | |||
| Canonical SMILES | C1=CC=C2C(=C1)C(=NN2C(=O)C3=C(C=CC=C3Cl)C(F)(F)F)C4=CC=C(C=C4)C(=O)O | ||||
| InChI | 1S/C22H12ClF3N2O3/c23-16-6-3-5-15(22(24,25)26)18(16)20(29)28-17-7-2-1-4-14(17)19(27-28)12-8-10-13(11-9-12)21(30)31/h1-11H,(H,30,31) | ||||
| InChIKey | DANLZOIRUUHIIX-UHFFFAOYSA-N | ||||
| PubChem Compound ID | 68159303 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 6T4I ROR(gamma)t ligand binding domain in complex with cholesterol and allosteric ligand MRL871 | ||||||
| Method | X-ray diffraction | Resolution | 1.84 Å | Mutation | No | [1] |
| PDB Sequence |
LTEIEHLVQS
276 VCKSYRETCQ286 LRLEDLLRQR296 SNIFSREEVT306 GYQRKSMWEM316 WERCAHHLTE 326 AIQYVVEFAK336 RLSGFMELCQ346 NDQIVLLKAG356 AMEVVLVRMC366 RAYNADNRTV 376 FFEGKYGGME386 LFRALGCSEL396 ISSIFDFSHS406 LSALHFSEDE416 IALYTALVLI 426 NAHRPGLQEK436 RKVEQLQYNL446 ELAFHHHLHK456 THRQSILAKL466 PPKGKLRSLC 476 SQHVERLQIF486 QHLHPIVVQA496 AFPPLYKELF506 S
|
|||||
|
|
TRP317
3.800
ALA321
3.705
LEU324
3.562
THR325
3.082
ILE328
3.468
GLN329
2.816
LEU353
3.638
LYS354
3.575
ALA357
4.073
MET358
3.531
VAL480
3.812
LEU483
3.284
GLN484
3.147
|
|||||
| PDB ID: 6T4K ROR(gamma)t ligand binding domain in complex with desmosterol and allosteric ligand MRL871 | ||||||
| Method | X-ray diffraction | Resolution | 1.89 Å | Mutation | No | [1] |
| PDB Sequence |
LTEIEHLVQS
276 VCKSYRETCQ286 LRLEDLLRQR296 SNIFSREEVT306 GYQRKSMWEM316 WERCAHHLTE 326 AIQYVVEFAK336 RLSGFMELCQ346 NDQIVLLKAG356 AMEVVLVRMC366 RAYNADNRTV 376 FFEGKYGGME386 LFRALGCSEL396 ISSIFDFSHS406 LSALHFSEDE416 IALYTALVLI 426 NAHRPGLQEK436 RKVEQLQYNL446 ELAFHHHLHK456 THRQSILAKL466 PPKGKLRSLC 476 SQHVERLQIF486 QHLHPIVVQA496 AFPPLYKELF506 S
|
|||||
|
|
TRP317
4.004
ALA321
3.652
LEU324
3.552
THR325
3.087
ILE328
3.546
GLN329
2.761
LEU353
3.632
LYS354
3.544
ALA357
4.060
MET358
3.573
VAL480
3.820
LEU483
3.326
GLN484
3.109
|
|||||
| PDB ID: 6T4Y ROR(gamma)t ligand binding domain in complex with 25-hydroxycholesterol and allosteric ligand MRL871 | ||||||
| Method | X-ray diffraction | Resolution | 1.95 Å | Mutation | No | [1] |
| PDB Sequence |
LTEIEHLVQS
276 VCKSYRETCQ286 LRLEDLLRQR296 SNIFSREEVT306 GYQRKSMWEM316 WERCAHHLTE 326 AIQYVVEFAK336 RLSGFMELCQ346 NDQIVLLKAG356 AMEVVLVRMC366 RAYNADNRTV 376 FFEGKYGGME386 LFRALGCSEL396 ISSIFDFSHS406 LSALHFSEDE416 IALYTALVLI 426 NAHRPGLQEK436 RKVEQLQYNL446 ELAFHHHLHK456 THRQSILAKL466 PPKGKLRSLC 476 SQHVERLQIF486 QHLHPIVVQA496 AFPPLYKELF506 S
|
|||||
|
|
TRP317
3.774
ALA321
3.718
LEU324
3.603
THR325
3.161
ILE328
3.504
GLN329
2.823
LEU353
3.602
LYS354
3.588
ALA357
3.939
MET358
3.688
VAL480
3.737
LEU483
3.150
GLN484
3.128
|
|||||
| PDB ID: 4YPQ Crystal structure of the ROR(gamma)t ligand binding domain in complex with 4-(1-(2-chloro-6-(trifluoromethyl)benzoyl)-1H-indazol-3-yl)benzoic acid | ||||||
| Method | X-ray diffraction | Resolution | 2.32 Å | Mutation | No | [2] |
| PDB Sequence |
ASLTEIEHLV
274 QSVCKSYRET284 CQLRLEDLLR294 QRSNIFSREE304 VTGYQRKSMW314 EMWERCAHHL 324 TEAIQYVVEF334 AKRLSGFMEL344 CQNDQIVLLK354 AGAMEVVLVR364 MCRAYNADNR 374 TVFFEGKYGG384 MELFRALGCS394 ELISSIFDFS404 HSLSALHFSE414 DEIALYTALV 424 LINAHRPGLQ434 EKRKVEQLQY444 NLELAFHHHL454 CKTHRQSILA464 KLPPKGKLRS 474 LCSQHVERLQ484 IFQHLHPIVV494 QAAFPPLYKE504 LFS
|
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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 .4F1 or .4F12 or .4F13 or :34F1;style chemicals stick;color identity;select .A:317 or .A:321 or .A:324 or .A:325 or .A:328 or .A:329 or .A:353 or .A:354 or .A:357 or .A:358 or .A:480 or .A:483 or .A:484 or .A:487 or .A:492 or .A:494 or .A:495 or .A:496 or .A:497 or .A:498 or .A:499 or .A:501 or .A:502 or .A:505 or .A:506; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
TRP317
3.643
ALA321
3.605
LEU324
3.675
THR325
3.180
ILE328
3.560
GLN329
2.986
LEU353
3.852
LYS354
3.933
ALA357
4.260
MET358
4.043
VAL480
3.944
LEU483
3.122
GLN484
3.158
|
|||||
| PDB ID: 5C4O Identification of a Novel Allosteric Binding Site for RORgt Inhibitors | ||||||
| Method | X-ray diffraction | Resolution | 2.24 Å | Mutation | No | [2] |
| PDB Sequence |
LTEIEHLVQS
276 VCKSYRETCQ286 LRLEDLLRQR296 SNIFSREEVT306 GYQRKSMWEM316 WERCAHHLTE 326 AIQYVVEFAK336 RLSGFMELCQ346 NDQIVLLKAG356 AMEVVLVRMC366 RAYNADNRTV 376 FFEGKYGGME386 LFRALGCSEL396 ISSIFDFSHS406 LSALHFSEDE416 IALYTALVLI 426 NAHRPGLQEK436 RKVEQLQYNL446 ELAFHHHLHK456 THRQSILAKL466 PPKGKLRSLC 476 SQHVERLQIF486 QHLHPIVVQA496 AFPPLYKELF506 S
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .4F1 or .4F12 or .4F13 or :34F1;style chemicals stick;color identity;select .A:317 or .A:321 or .A:324 or .A:325 or .A:328 or .A:329 or .A:353 or .A:354 or .A:357 or .A:358 or .A:480 or .A:483 or .A:484 or .A:487 or .A:492 or .A:494 or .A:495 or .A:496 or .A:497 or .A:498 or .A:499 or .A:501 or .A:502 or .A:505 or .A:506; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
TRP317
3.704
ALA321
3.741
LEU324
3.572
THR325
3.388
ILE328
3.604
GLN329
2.831
LEU353
3.575
LYS354
3.748
ALA357
4.045
MET358
3.464
VAL480
3.785
LEU483
3.335
GLN484
3.199
|
|||||
| PDB ID: 6T4U ROR(gamma)t ligand binding domain in complex with 20-alpha-hydroxycholesterol and allosteric ligand MRL871 | ||||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [1] |
| PDB Sequence |
TEIEHLVQSV
277 CKSYRETCQL287 RLEDLLRQRS297 NIFSREEVTG307 YQRKSMWEMW317 ERCAHHLTEA 327 IQYVVEFAKR337 LSGFMELCQN347 DQIVLLKAGA357 MEVVLVRMCR367 AYNADNRTVF 377 FEGKYGGMEL387 FRALGCSELI397 SSIFDFSHSL407 SALHFSEDEI417 ALYTALVLIN 427 AHRPGLQEKR437 KVEQLQYNLE447 LAFHHHLHKT457 HRQSILAKLP467 PKGKLRSLCS 477 QHVERLQIFQ487 HLHPIVVQAA497 FPPLYKELFS507
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .4F1 or .4F12 or .4F13 or :34F1;style chemicals stick;color identity;select .A:317 or .A:321 or .A:324 or .A:325 or .A:328 or .A:329 or .A:353 or .A:354 or .A:357 or .A:358 or .A:480 or .A:483 or .A:484 or .A:487 or .A:492 or .A:494 or .A:495 or .A:496 or .A:497 or .A:498 or .A:499 or .A:501 or .A:502 or .A:505 or .A:506; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
TRP317
3.853
ALA321
3.708
LEU324
3.559
THR325
3.202
ILE328
3.474
GLN329
2.930
LEU353
3.675
LYS354
3.592
ALA357
4.021
MET358
3.579
VAL480
3.813
LEU483
3.270
GLN484
3.038
|
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Cooperativity between the orthosteric and allosteric ligand binding sites of RORGammat. Proc Natl Acad Sci U S A. 2021 Feb 9;118(6):e2021287118. | ||||
| REF 2 | Identification of an allosteric binding site for RORGammat inhibition. Nat Commun. 2015 Dec 7;6:8833. | ||||
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