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 25-hydroxycholesterol Ligand Info
Canonical SMILES CC(CCCC(C)(C)O)C1CCC2C1(CCC3C2CC=C4C3(CCC(C4)O)C)C
InChI 1S/C27H46O2/c1-18(7-6-14-25(2,3)29)22-10-11-23-21-9-8-19-17-20(28)12-15-26(19,4)24(21)13-16-27(22,23)5/h8,18,20-24,28-29H,6-7,9-17H2,1-5H3/t18-,20+,21+,22-,23+,24+,26+,27-/m1/s1
InChIKey INBGSXNNRGWLJU-ZHHJOTBYSA-N
PubChem Compound ID 65094
Drug Binding Sites of Target  Top
PDB ID: 6T4X      ROR(gamma)t ligand binding domain in complex with 25-hydroxycholesterol and allosteric ligand FM26
Method X-ray diffraction Resolution 1.48 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)
CYS285
4.403
GLN286
2.949
LEU287
4.067
TRP317
4.939
CYS320
3.692
HIS323
3.720
LEU324
3.698
ALA327
4.121
VAL361
3.919
ARG364
3.872
MET365
3.696
ALA368
4.028
VAL376
4.069
Residue
Distance (Å)
PHE377
4.140
PHE378
3.926
PHE388
3.983
LEU391
3.717
CYS393
4.151
LEU396
3.827
ILE397
4.043
ILE400
4.060
PHE401
4.265
HIS479
2.954
ARG482
4.373
LEU483
3.283
PHE486
3.687
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)
CYS285
4.377
GLN286
2.947
LEU287
4.036
TRP317
4.545
CYS320
3.798
HIS323
3.776
LEU324
3.454
ALA327
3.956
VAL361
3.901
ARG364
3.813
MET365
3.671
ALA368
3.922
VAL376
3.941
Residue
Distance (Å)
PHE377
4.120
PHE378
3.950
PHE388
4.037
LEU391
3.727
CYS393
4.230
LEU396
3.675
ILE397
4.048
ILE400
4.187
PHE401
4.223
HIS479
2.922
ARG482
4.340
LEU483
3.175
PHE486
3.742
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
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)
CYS285
4.219
GLN286
2.949
LEU287
3.899
TRP317
4.443
CYS320
3.753
HIS323
3.721
LEU324
3.335
ALA327
4.092
VAL361
3.909
ARG364
3.829
MET365
3.647
ALA368
4.011
VAL376
4.023
Residue
Distance (Å)
PHE377
4.102
PHE378
4.004
PHE388
3.949
LEU391
3.678
CYS393
4.095
LEU396
3.742
ILE397
4.130
ILE400
4.078
PHE401
4.263
HIS479
3.051
ARG482
4.516
LEU483
3.240
PHE486
3.714
PDB ID: 3L0L      Crystal structure of orphan nuclear receptor RORgamma in complex with natural ligand
Method X-ray diffraction Resolution 1.74 Å Mutation No [2]
PDB Sequence
EAPYASLTEI
270
EHLVQSVCKS
280
YRETCQLRLE
290
DLLRQRSNIF
300
SREEVTGYQR
310

KSMWEMWERC
320
AHHLTEAIQY
330
VVEFAKRLSG
340
FMELCQNDQI
350
VLLKAGAMEV
360

VLVRMCRAYN
370
ADNRTVFFEG
380
KYGGMELFRA
390
LGCSELISSI
400
FDFSHSLSAL
410

HFSEDEIALY
420
TALVLINAHR
430
PGLQEKRKVE
440
QLQYNLELAF
450
HHHLCKTHRQ
460

SILAKLPPKG
470
KLRSLCSQHV
480
ERLQIFQHLH
490
PIVVQAAFPP
500
LYKELFS
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .HC3 or .HC32 or .HC33 or :3HC3;style chemicals stick;color identity;select .A:285 or .A:286 or .A:287 or .A:317 or .A:320 or .A:323 or .A:324 or .A:327 or .A:358 or .A:361 or .A:364 or .A:365 or .A:367 or .A:368 or .A:376 or .A:377 or .A:378 or .A:388 or .A:391 or .A:393 or .A:396 or .A:397 or .A:400 or .A:401 or .A:479 or .A:482 or .A:502; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
CYS285
4.521
GLN286
3.038
LEU287
3.749
TRP317
3.514
CYS320
3.783
HIS323
3.657
LEU324
3.566
ALA327
3.875
MET358
4.516
VAL361
3.970
ARG364
3.814
MET365
3.615
ARG367
4.959
ALA368
3.807
Residue
Distance (Å)
VAL376
4.196
PHE377
3.741
PHE378
4.049
PHE388
3.806
LEU391
3.596
CYS393
4.003
LEU396
3.623
ILE397
3.687
ILE400
3.560
PHE401
4.388
HIS479
2.970
ARG482
4.663
TYR502
4.636
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 Structural basis for hydroxycholesterols as natural ligands of orphan nuclear receptor RORgamma. Mol Endocrinol. 2010 May;24(5):923-9.

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