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 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
RORG_HUMAN
Ligand General Information  Top
Ligand Name 4-[1-[2,6-Bis(chloranyl)phenyl]carbonyl-5-methyl-thieno[3,2-c]pyrazol-3-yl]benzoic acid Ligand Info
Canonical SMILES CC1=CC2=C(S1)C(=NN2C(=O)C3=C(C=CC=C3Cl)Cl)C4=CC=C(C=C4)C(=O)O
InChI 1S/C20H12Cl2N2O3S/c1-10-9-15-18(28-10)17(11-5-7-12(8-6-11)20(26)27)23-24(15)19(25)16-13(21)3-2-4-14(16)22/h2-9H,1H3,(H,26,27)
InChIKey LDKVVDVRWBVBGM-UHFFFAOYSA-N
PubChem Compound ID 90466288
Drug Binding Sites of Target  Top
PDB ID: 6TLQ      ROR(gamma)t ligand binding domain in complex with cholesterol and allosteric ligand Glenmark
Method X-ray diffraction Resolution 1.76 Å Mutation No [1]
PDB Sequence
TEIEHLVQSV
277
CKSYRETCQL
287
RLEDLLRQRS
297
NIFSREEVTG
307
YQRKSMWEMW
317

ERCAHHLTEA
327
IQYVVEFAKR
337
LSGFMELCQN
347
DQIVLLKAGA
357
MEVVLVRMCR
367

AYNADNRTVF
377
FEGKYGGMEL
387
FRALGCSELI
397
SSIFDFSHSL
407
SALHFSEDEI
417

ALYTALVLIN
427
AHRPGLQEKR
437
KVEQLQYNLE
447
LAFHHHLHKT
457
HRQSILAKLP
467

PKGKLRSLCS
477
QHVERLQIFQ
487
HLHPIVVQAA
497
FPPLYKELFS
507
Residue
Distance (Å)
TRP317
3.688
ALA321
3.858
LEU324
3.542
THR325
3.560
ILE328
3.650
GLN329
2.751
LEU353
3.654
LYS354
3.179
ALA357
4.238
MET358
3.526
VAL480
3.908
LEU483
3.437
GLN484
3.434
Residue
Distance (Å)
GLN487
4.116
ILE492
4.192
VAL494
3.992
GLN495
3.639
ALA496
3.581
ALA497
2.877
PHE498
2.881
PRO499
4.445
LEU501
3.822
TYR502
3.445
LEU505
3.504
PHE506
3.531
PDB ID: 6T50      ROR(gamma)t ligand binding domain in complex with 25-hydroxycholesterol and allosteric ligand Glenmark
Method X-ray diffraction Resolution 1.87 Å Mutation No [1]
PDB Sequence
LTEIEHLVQS
276
VCKSYRETCQ
286
LRLEDLLRQR
296
SNIFSREEVT
306
GYQRKSMWEM
316

WERCAHHLTE
326
AIQYVVEFAK
336
RLSGFMELCQ
346
NDQIVLLKAG
356
AMEVVLVRMC
366

RAYNADNRTV
376
FFEGKYGGME
386
LFRALGCSEL
396
ISSIFDFSHS
406
LSALHFSEDE
416

IALYTALVLI
426
NAHRPGLQEK
436
RKVEQLQYNL
446
ELAFHHHLHK
456
THRQSILAKL
466

PPKGKLRSLC
476
SQHVERLQIF
486
QHLHPIVVQA
496
AFPPLYKELF
506
S
Residue
Distance (Å)
TRP317
3.858
ALA321
3.622
LEU324
3.527
THR325
3.057
ILE328
3.526
GLN329
2.739
VAL332
4.996
LEU353
3.710
LYS354
3.014
ALA355
4.879
ALA357
4.232
MET358
3.841
VAL480
4.006
LEU483
3.328
Residue
Distance (Å)
GLN484
3.839
GLN487
3.968
ILE492
3.998
VAL494
4.176
GLN495
4.196
ALA496
3.409
ALA497
2.796
PHE498
2.802
PRO499
4.381
LEU501
3.829
TYR502
3.821
LEU505
2.759
PHE506
3.795
PDB ID: 6TLT      ROR(gamma)t ligand binding domain in complex with desmosterol and allosteric ligand Glenmark
Method X-ray diffraction Resolution 2.11 Å Mutation No [1]
PDB Sequence
TEIEHLVQSV
277
CKSYRETCQL
287
RLEDLLRQRS
297
NIFSREEVTG
307
YQRKSMWEMW
317

ERCAHHLTEA
327
IQYVVEFAKR
337
LSGFMELCQN
347
DQIVLLKAGA
357
MEVVLVRMCR
367

AYNADNRTVF
377
FEGKYGGMEL
387
FRALGCSELI
397
SSIFDFSHSL
407
SALHFSEDEI
417

ALYTALVLIN
427
AHRPGLQEKR
437
KVEQLQYNLE
447
LAFHHHLHKT
457
HRQSILAKLP
467

PKGKLRSLCS
477
QHVERLQIFQ
487
HLHPIVVQAA
497
FPPLYKELFS
507
Residue
Distance (Å)
TRP317
3.799
ALA321
3.904
LEU324
3.583
THR325
2.938
ILE328
3.407
GLN329
2.656
VAL332
4.908
LEU353
3.581
LYS354
3.276
ALA355
5.000
GLY356
4.826
ALA357
4.050
MET358
3.467
VAL480
3.757
Residue
Distance (Å)
LEU483
3.243
GLN484
3.664
GLN487
4.092
ILE492
3.893
VAL494
4.157
GLN495
4.361
ALA496
3.493
ALA497
2.940
PHE498
3.009
PRO499
4.702
LEU501
3.682
TYR502
3.819
LEU505
3.330
PHE506
3.434
PDB ID: 6TLM      ROR(gamma)t ligand binding domain in complex with allosteric ligand compound 13 (Glenmark)
Method X-ray diffraction Resolution 2.32 Å Mutation No [2]
PDB Sequence
LTEIEHLVQS
276
VCKSYRETCQ
286
LRLEDLLRQR
296
SNIFSREEVT
306
GYQRKSMWEM
316

WERCAHHLTE
326
AIQYVVEFAK
336
RLSGFMELCQ
346
NDQIVLLKAG
356
AMEVVLVRMC
366

RAYNADNRTV
376
FFEGKYGGME
386
LFRALGCSEL
396
ISSIFDFSHS
406
LSALHFSEDE
416

IALYTALVLI
426
NAHRPGLQEK
436
RKVEQLQYNL
446
ELAFHHHLHK
456
THRQSILAKL
466

PPKGKLRSLC
476
SQHVERLQIF
486
QHLHPIVVQA
496
AFPPLYKELF
506
S
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .MJE or .MJE2 or .MJE3 or :3MJE;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
Residue
Distance (Å)
TRP317
3.735
ALA321
3.825
LEU324
3.335
THR325
3.462
ILE328
3.382
GLN329
2.713
LEU353
3.640
LYS354
3.187
ALA357
4.072
MET358
3.507
VAL480
4.151
LEU483
3.747
GLN484
3.823
Residue
Distance (Å)
GLN487
4.317
ILE492
4.022
VAL494
4.050
GLN495
3.604
ALA496
3.388
ALA497
3.021
PHE498
3.066
PRO499
4.592
LEU501
3.964
TYR502
3.370
LEU505
3.271
PHE506
3.450
PDB ID: 6T4W      ROR(gamma)t ligand binding domain in complex with 20-alpha-hydroxycholesterol and allosteric ligand Glenmark
Method X-ray diffraction Resolution 1.71 Å Mutation No [1]
PDB Sequence
TEIEHLVQSV
277
CKSYRETCQL
287
RLEDLLRQRS
297
NIFSREEVTG
307
YQRKSMWEMW
317

ERCAHHLTEA
327
IQYVVEFAKR
337
LSGFMELCQN
347
DQIVLLKAGA
357
MEVVLVRMCR
367

AYNADNRTVF
377
FEGKYGGMEL
387
FRALGCSELI
397
SSIFDFSHSL
407
SALHFSEDEI
417

ALYTALVLIN
427
AHRPGLQEKR
437
KVEQLQYNLE
447
LAFHHHLHKT
457
HRQSILAKLP
467

PKGKLRSLCS
477
QHVERLQIFQ
487
HLHPIVVQAA
497
FPPLYKELFS
507
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .MJE or .MJE2 or .MJE3 or :3MJE;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:355 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
Residue
Distance (Å)
TRP317
3.679
ALA321
3.908
LEU324
3.501
THR325
3.414
ILE328
3.619
GLN329
2.757
LEU353
3.548
LYS354
3.118
ALA355
4.913
ALA357
4.153
MET358
3.572
VAL480
3.955
LEU483
3.391
Residue
Distance (Å)
GLN484
3.428
GLN487
3.980
ILE492
4.340
VAL494
3.907
GLN495
3.525
ALA496
3.398
ALA497
2.710
PHE498
2.757
PRO499
4.320
LEU501
3.816
TYR502
3.521
LEU505
3.606
PHE506
3.594
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 Elucidation of an Allosteric Mode of Action for a Thienopyrazole RORGammat Inverse Agonist. ChemMedChem. 2020 Apr 3;15(7):561-565.

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