Target Binding Site Detail

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Target General Information
Ligand General Information
Drug Binding Sites of Target
References
Target General Information  Top
Target ID T51426 Target Info
Target Name Farnesoid X-activated receptor (FXR)
Synonyms Retinoid X receptor-interacting protein 14; RXR-interacting protein 14; RIP14; Nuclear receptor subfamily 1 group H member 4; HRR1; Farnesol receptor HRR-1; FXR; Bile acid receptor; BAR
Target Type Successful Target
Gene Name NR1H4
Biochemical Class Nuclear hormone receptor
UniProt ID
NR1H4_HUMAN
Ligand General Information  Top
Ligand Name GW4064 Ligand Info
Canonical SMILES CC(C)C1=C(C(=NO1)C2=C(C=CC=C2Cl)Cl)COC3=CC(=C(C=C3)C=CC4=CC(=CC=C4)C(=O)O)Cl
InChI 1S/C28H22Cl3NO4/c1-16(2)27-21(26(32-36-27)25-22(29)7-4-8-23(25)30)15-35-20-12-11-18(24(31)14-20)10-9-17-5-3-6-19(13-17)28(33)34/h3-14,16H,15H2,1-2H3,(H,33,34)/b10-9+
InChIKey BYTNEISLBIENSA-MDZDMXLPSA-N
PubChem Compound ID 9893571
Drug Binding Sites of Target  Top
PDB ID: 3DCT      FXR with SRC1 and GW4064
Method X-ray diffraction Resolution 2.50 Å Mutation No [1]
PDB Sequence
ELTPDQQTLL
253
HFIMDSYNKQ
263
RMPQEITNKI
273
LKEEFSAEEN
283
FLILTEMATN
293

HVQVLVEFTK
303
KLPGFQTLDH
313
EDQIALLKGS
323
AVEAMFLRSA
333
EIFNKKLPSG
343

HSDLLEERIR
353
NSGISDEYIT
363
PMFSFYKSIG
373
ELKMTQEEYA
383
LLTAIVILSP
393

DRQYIKDREA
403
VEKLQEPLLD
413
VLQKLCKIHQ
423
PENPQHFACL
433
LGRLTELRTF
443

NHHHAEMLMS
453
WRVNDHKFTP
463
LLCEIWDVQ
Residue
Distance (Å)
ARG264
3.789
MET265
3.176
THR270
3.595
ILE273
4.671
PHE284
3.705
LEU287
3.413
THR288
3.473
MET290
2.856
ALA291
3.396
HIS294
3.050
VAL325
4.077
MET328
3.587
PHE329
3.349
ARG331
2.841
Residue
Distance (Å)
SER332
4.226
ILE335
3.696
SER342
3.343
GLY343
4.052
LEU348
4.891
ILE352
3.807
ILE357
3.912
MET365
3.761
TYR369
3.669
HIS447
3.409
TRP454
3.215
PHE461
4.478
LEU465
4.105
TRP469
3.747
PDB ID: 6A60      Crystal structure of human FXR/RXR-LBD heterodimer bound to GW4064 and 9cRA and SRC1
Method X-ray diffraction Resolution 3.05 Å Mutation Yes [2]
PDB Sequence
ELTPDQQTLL
253
HFIMDSYNKQ
263
RMPQEITNKF
278
SAEENFLILT
288
EMATNHVQVL
298

VEFTKKLPGF
308
QTLDHEDQIA
318
LLKGSAVEAM
328
FLRSAEIFNK
338
KLSDLLEERI
352

RNSGISDEYI
362
TPMFSFYKSI
372
GELKMTQEEY
382
ALLTAIVILS
392
PDRQYIKDRE
402

AVEKLQEPLL
412
DVLQKLCKIH
422
QPENPQHFAE
432
LLGRLTELRT
442
FNHHHAEMLM
452

SWRVNDHKFT
462
PLLEEIWDV
Residue
Distance (Å)
GLN263
3.253
ARG264
3.604
MET265
4.098
PHE284
3.798
LEU287
3.819
THR288
3.841
MET290
3.870
ALA291
3.795
HIS294
3.182
VAL297
4.581
VAL325
4.505
MET328
3.132
PHE329
3.358
ARG331
2.875
Residue
Distance (Å)
SER332
3.588
ILE335
3.449
LEU348
4.734
ILE352
4.431
ILE357
3.997
MET365
3.674
TYR369
3.264
HIS447
3.223
MET450
4.183
LEU451
3.853
TRP454
3.186
PHE461
3.494
LEU465
3.468
TRP469
3.812
References  Top
REF 1 Conformationally constrained farnesoid X receptor (FXR) agonists: Naphthoic acid-based analogs of GW 4064. Bioorg Med Chem Lett. 2008 Aug 1;18(15):4339-43.
REF 2 Ligand binding and heterodimerization with retinoid X receptor Alpha (RXRAlpha) induce farnesoid X receptor (FXR) conformational changes affecting coactivator binding. J Biol Chem. 2018 Nov 23;293(47):18180-18191.

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