Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T52297 | Target Info | |||
| Target Name | Oxysterols receptor LXR-alpha (NR1H3) | ||||
| Synonyms | Nuclear receptor subfamily 1 group H member 3; Nuclear receptor LXRalpha; Nuclear orphan receptor LXR-alpha; Liver X receptor alpha; LXRalpha; LXRA | ||||
| Target Type | Patented-recorded Target | ||||
| Gene Name | NR1H3 | ||||
| Biochemical Class | Nuclear hormone receptor | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: GW-3965 | Ligand Info | |||||
| Structure Description | X-ray structure of GW3965 synthetic agonist bound to the LXR-alpha | PDB:3IPQ | ||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [1] |
| PDB Sequence |
QLSPEQLGMI
214 EKLVAAQQTP237 WPEARQQRFA255 HFTELAIVSV265 QEIVDFAKQL275 PGFLQLSRED 285 QIALLKTSAI295 EVMLLETSRR305 YNPGSESITF315 LKDFSYNRED325 FAKAGLQVEF 335 INPIFEFSRA345 MNELQLNDAE355 FALLIAISIF365 SADRPNVQDQ375 LQVERLQHTY 385 VEALHAYVSI395 HHPHDRLMFP405 RMLMKLVSLR415 TLSSVHSEQV425 FALRLQDKKL 435 PPLLSEIWDV445
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PHE254
4.197
PHE257
3.554
THR258
3.873
LEU260
3.396
ALA261
3.613
VAL263
4.494
SER264
3.573
GLU267
3.762
ILE295
3.747
MET298
3.559
LEU299
3.623
GLU301
4.050
THR302
3.151
ARG305
2.857
ILE313
3.754
THR314
4.348
|
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| Ligand Name: L-783483 | Ligand Info | |||||
| Structure Description | X-ray structure of benzisoxazole synthetic agonist bound to the LXR-alpha | PDB:3IPS | ||||
| Method | X-ray diffraction | Resolution | 2.26 Å | Mutation | No | [1] |
| PDB Sequence |
QLSPEQLGMI
214 EKLVAAQQVT236 PWPSREARQQ252 RFAHFTELAI262 VSVQEIVDFA272 KQLPGFLQLS 282 REDQIALLKT292 SAIEVMLLET302 SRRYNPGSES312 ITFLKDFSYN322 REDFAKAGLQ 332 VEFINPIFEF342 SRAMNELQLN352 DAEFALLIAI362 SIFSADRPNV372 QDQLQVERLQ 382 HTYVEALHAY392 VSIHHPHDRL402 MFPRMLMKLV412 SLRTLSSVHS422 EQVFALRLQD 432 KKLPPLLSEI442 WDVH
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PHE254
4.177
PHE257
3.307
THR258
3.810
LEU260
2.958
ALA261
3.861
VAL263
4.808
SER264
3.776
GLU267
4.245
ILE295
4.142
MET298
3.345
LEU299
3.986
GLU301
3.320
THR302
3.320
ARG305
2.829
|
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| Ligand Name: T0901317 | Ligand Info | |||||
| Structure Description | Crystal structure of the LXRalfa-RXRbeta LBD heterodimer | PDB:1UHL | ||||
| Method | X-ray diffraction | Resolution | 2.90 Å | Mutation | No | [2] |
| PDB Sequence |
MSPEQLGMIE
215 KLVAAQQQCN225 RRSFEARQQR253 FAHFTELAIV263 SVQEIVDFAK273 QLPGFLQLSR 283 EDQIALLKTS293 AIEVMLLETS303 RRYNPGSESI313 TDFSYNREDF326 AKAGLQVEFI 336 NPIFEFSRAM346 NELQLNDAEF356 ALLIAISIFS366 ADRPNVQDQL376 QVERLQHTYV 386 EALHAYVSIH396 HPHDRLMFPR406 MLMKLVSLRT416 LSSVHSEQVF426 ALRLQDKKLP 436 PLLSEIWDV
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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 .444 or .4442 or .4443 or :3444;style chemicals stick;color identity;select .B:254 or .B:257 or .B:258 or .B:260 or .B:261 or .B:264 or .B:295 or .B:298 or .B:299 or .B:302 or .B:305 or .B:326 or .B:331 or .B:335 or .B:339 or .B:421 or .B:424 or .B:425 or .B:428 or .B:439 or .B:443; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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PHE254
4.070
PHE257
3.795
THR258
4.120
LEU260
3.924
ALA261
3.374
SER264
2.837
ILE295
4.339
MET298
2.882
LEU299
3.528
THR302
2.431
ARG305
4.956
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| Ligand Name: 2-Chloro-4-{1'-[(2r)-2-Hydroxy-3-Methyl-2-(Trifluoromethyl)butanoyl]-4,4'-Bipiperidin-1-Yl}-N,N-Dimethylbenzamide | Ligand Info | |||||
| Structure Description | Identification of LXRbeta selective agonists for the treatment of Alzheimer's Disease | PDB:5HJS | ||||
| Method | X-ray diffraction | Resolution | 1.72 Å | Mutation | No | [3] |
| PDB Sequence |
QLSPEQLGMI
50 EKLVAAQQLR70 VTPWPSREAR86 QQRFAHFTEL96 AIVSVQEIVD106 FAKQLPGFLQ 116 LSREDQIALL126 KTSAIEVMLL136 ETSRRYNPGS146 ESITFLKDFS156 YNREDFAKAG 166 LQVEFINPIF176 EFSRAMNELQ186 LNDAEFALLI196 AISIFSADRP206 NVQDQLQVER 216 LQHTYVEALH226 AYVSIHHPHD236 RLMFPRMLMK246 LVSLRTLSSV256 HSEQVFALRL 266 QDKKLPPLLS276 EIWDVH
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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 .668 or .6682 or .6683 or :3668;style chemicals stick;color identity;select .A:90 or .A:93 or .A:94 or .A:96 or .A:97 or .A:99 or .A:100 or .A:103 or .A:131 or .A:134 or .A:135 or .A:137 or .A:138 or .A:141 or .A:150 or .A:151 or .A:152 or .A:165 or .A:166 or .A:167 or .A:171 or .A:257 or .A:260 or .A:261 or .A:264 or .A:271 or .A:275 or .A:279; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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PHE90
3.788
PHE93
3.650
THR94
3.487
LEU96
3.374
ALA97
3.659
VAL99
4.047
SER100
3.872
GLU103
3.435
ILE131
3.757
MET134
3.579
LEU135
4.921
GLU137
4.071
THR138
3.437
ARG141
2.890
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| Ligand Name: 4-{[Methyl(3-{[7-propyl-3-(trifluoromethyl)-1,2-benzisoxazol-6-yl]oxy}propyl)carbamoyl]amino}benzoic acid | Ligand Info | |||||
| Structure Description | X-ray structure of benzisoxazole urea synthetic agonist bound to the LXR-alpha | PDB:3IPU | ||||
| Method | X-ray diffraction | Resolution | 2.40 Å | Mutation | No | [1] |
| PDB Sequence |
PQLSPEQLGM
213 IEKLVAAQQQ223 CNRRSFSDRL233 RVTPWPPHSR247 EARQQRFAHF257 TELAIVSVQE 267 IVDFAKQLPG277 FLQLSREDQI287 ALLKTSAIEV297 MLLETSRRYN307 PGSESITFLK 317 DFSYNREDFA327 KAGLQVEFIN337 PIFEFSRAMN347 ELQLNDAEFA357 LLIAISIFSA 367 DRPNVQDQLQ377 VERLQHTYVE387 ALHAYVSIHH397 PHDRLMFPRM407 LMKLVSLRTL 417 SSVHSEQVFA427 LRLQDKKLPP437 LLSEIWDV
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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 .O40 or .O402 or .O403 or :3O40;style chemicals stick;color identity;select .A:225 or .A:232 or .A:254 or .A:257 or .A:258 or .A:260 or .A:261 or .A:264 or .A:267 or .A:295 or .A:298 or .A:299 or .A:301 or .A:302 or .A:305 or .A:315 or .A:316 or .A:317 or .A:326 or .A:331 or .A:335 or .A:339 or .A:421 or .A:424 or .A:425 or .A:428 or .A:435 or .A:439 or .A:443; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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ASN225
3.501
ARG232
3.044
PHE254
4.062
PHE257
3.313
THR258
3.782
LEU260
3.504
ALA261
3.608
SER264
3.870
GLU267
4.623
ILE295
3.794
MET298
3.780
LEU299
4.212
GLU301
4.005
THR302
3.809
ARG305
3.418
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| Ligand Name: Tert-Butyl 2-[[4-[ethanoyl(Methyl)amino]phenoxy]methyl]-5-(Trifluoromethyl)benzoate | Ligand Info | |||||
| Structure Description | Crystal structure of LXRalpha in complex with tert-butyl benzoate analog, compound 4 | PDB:5AVI | ||||
| Method | X-ray diffraction | Resolution | 2.70 Å | Mutation | No | [4] |
| PDB Sequence |
PQLSPEQLGM
213 IEKLVAAQQR234 VTPWPPHSRE248 ARQQRFAHFT258 ELAIVSVQEI268 VDFAKQLPGF 278 LQLSREDQIA288 LLKTSAIEVM298 LLETSRRYNP308 GSESITFLKD318 FSYNREDFAK 328 AGLQVEFINP338 IFEFSRAMNE348 LQLNDAEFAL358 LIAISIFSAD368 RPNVQDQLQV 378 ERLQHTYVEA388 LHAYVSIHHP398 HDRLMFPRML408 MKLVSLRTLS418 SVHSEQVFAL 428 RLQDKKLPPL438 LSEIWDVH
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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 .4KM or .4KM2 or .4KM3 or :34KM;style chemicals stick;color identity;select .A:254 or .A:257 or .A:258 or .A:260 or .A:261 or .A:264 or .A:295 or .A:298 or .A:299 or .A:301 or .A:302 or .A:305 or .A:315 or .A:326 or .A:331 or .A:335 or .A:339 or .A:421 or .A:424 or .A:425 or .A:428 or .A:435 or .A:439 or .A:443; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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PHE254
4.120
PHE257
3.383
THR258
3.861
LEU260
3.525
ALA261
3.455
SER264
3.624
ILE295
3.399
MET298
3.701
LEU299
3.855
GLU301
3.724
THR302
3.599
ARG305
3.492
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| Ligand Name: 2-[4-[4-[[2-[(2-Methylpropan-2-Yl)oxycarbonyl]-3-Oxidanyl-4-(Trifluoromethyl)phenyl]methoxy]phenyl]phenyl]ethanoic Acid | Ligand Info | |||||
| Structure Description | Crystal structure of LXRalpha in complex with tert-butyl benzoate analog, compound 32b | PDB:5AVL | ||||
| Method | X-ray diffraction | Resolution | 2.80 Å | Mutation | No | [4] |
| PDB Sequence |
PQLSPEQLGM
213 IEKLVAAQQV235 TPWREARQQR253 FAHFTELAIV263 SVQEIVDFAK273 QLPGFLQLSR 283 EDQIALLKTS293 AIEVMLLETS303 RRYNPGSESI313 TFLKDFSYNR323 EDFAKAGLQV 333 EFINPIFEFS343 RAMNELQLND353 AEFALLIAIS363 IFSADRPNVQ373 DQLQVERLQH 383 TYVEALHAYV393 SIHHPHDRLM403 FPRMLMKLVS413 LRTLSSVHSE423 QVFALRLQDK 433 KLPPLLSEIW443 DVHE
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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 .4KQ or .4KQ2 or .4KQ3 or :34KQ;style chemicals stick;color identity;select .A:254 or .A:257 or .A:258 or .A:260 or .A:261 or .A:264 or .A:267 or .A:295 or .A:298 or .A:299 or .A:301 or .A:302 or .A:305 or .A:314 or .A:315 or .A:316 or .A:326 or .A:331 or .A:335 or .A:339 or .A:421 or .A:424 or .A:425 or .A:428 or .A:435 or .A:439 or .A:443; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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PHE254
3.655
PHE257
3.344
THR258
3.872
LEU260
3.579
ALA261
3.521
SER264
3.634
GLU267
4.366
ILE295
3.300
MET298
3.781
LEU299
3.680
GLU301
4.003
THR302
3.302
ARG305
2.930
THR314
4.205
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | X-ray structures of the LXRalpha LBD in its homodimeric form and implications for heterodimer signaling. J Mol Biol. 2010 May 28;399(1):120-32. | ||||
| REF 2 | Crystal structure of the heterodimeric complex of LXRalpha and RXRbeta ligand-binding domains in a fully agonistic conformation. EMBO J. 2003 Sep 15;22(18):4625-33. | ||||
| REF 3 | Identification and in Vivo Evaluation of Liver X Receptor beta-Selective Agonists for the Potential Treatment of Alzheimer's Disease. J Med Chem. 2016 Apr 14;59(7):3489-98. | ||||
| REF 4 | Discovery and structure-guided optimization of tert-butyl 6-(phenoxymethyl)-3-(trifluoromethyl)benzoates as liver X receptor agonists. Bioorg Med Chem Lett. 2015 Sep 15;25(18):3914-20. | ||||
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