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 T02506 Target Info
Target Name HUMAN estrogen receptor (ESR1)
Synonyms Nuclear receptor subfamily 3 group A member 1; NR3A1; Estradiol receptor; ESR; ER-alpha; ER
Gene Name ESR1
Biochemical Class Nuclear hormone receptor
UniProt ID
ESR1_HUMAN
Ligand General Information  Top
Ligand Name Bazedoxifene Ligand Info
Canonical SMILES CC1=C(N(C2=C1C=C(C=C2)O)CC3=CC=C(C=C3)OCCN4CCCCCC4)C5=CC=C(C=C5)O
InChI 1S/C30H34N2O3/c1-22-28-20-26(34)12-15-29(28)32(30(22)24-8-10-25(33)11-9-24)21-23-6-13-27(14-7-23)35-19-18-31-16-4-2-3-5-17-31/h6-15,20,33-34H,2-5,16-19,21H2,1H3
InChIKey UCJGJABZCDBEDK-UHFFFAOYSA-N
PubChem Compound ID 154257
Drug Binding Sites of Target  Top
PDB ID: 6PSJ      Bazedoxifene in Complex with Y537S Estrogen Receptor Alpha Ligand Binding Domain
Method X-ray diffraction Resolution 1.80 Å Mutation Yes [1]
PDB Sequence
ALSLTADQMV
316
SALLDAEPPI
326
LYSESMMGLL
346
TNLADRELVH
356
MINWAKRVPG
366

FVDLTLHDQV
376
HLLESAWLEI
386
LMIGLVWRSM
396
EHPGKLLFAP
406
NLLLDRNQGK
416

SVEGMVEIFD
426
MLLATSSRFR
436
MMNLQGEEFV
446
CLKSIILLNS
456
GVYTFLSSTL
466

KSLEEKDHIH
476
RVLDKITDTL
486
IHLMAKAGLT
496
LQQQHQRLAQ
506
LLLILSHIRH
516

MSNKGMEHLY
526
SMKNVVPLSD
538
LLLEMLDAHR
548
LH
Residue
Distance (Å)
MET343
4.028
LEU346
3.626
THR347
3.773
LEU349
3.774
ALA350
3.815
ASP351
2.637
GLU353
2.295
LEU354
3.803
TRP383
3.693
LEU384
4.113
LEU387
3.815
MET388
3.756
Residue
Distance (Å)
LEU391
3.792
ARG394
2.967
PHE404
3.563
MET421
4.069
ILE424
3.811
LEU428
4.378
GLY521
3.860
HIS524
2.204
LEU525
3.679
MET528
4.868
LEU536
4.035
PDB ID: 4XI3      Estrogen Receptor Alpha Ligand Binding Domain in Complex with Bazedoxifene
Method X-ray diffraction Resolution 2.49 Å Mutation Yes [2]
PDB Sequence
LALSLTADQM
315
VSALLDAEPP
325
ILYSEYDPSM
342
MGLLTNLADR
352
ELVHMINWAK
362

RVPGFVDLTS
372
HDQVHLLECA
382
WLEILMIGLV
392
WRSMEHPGKL
402
LFAPNLLLDR
412

NQGKCVEGMV
422
EIFDMLLATS
432
SRFRMMNLQG
442
EEFVCLKSII
452
LLNSGVYTST
465

LKSLEEKDHI
475
HRVLDKITDT
485
LIHLMAKAGL
495
TLQQQHQRLA
505
QLLLILSHIR
515

HMSNKGMEHL
525
YSMKCKNVVP
535
SYDLLLEMLD
545
Residue
Distance (Å)
MET343
4.047
LEU346
3.613
THR347
3.627
LEU349
4.447
ALA350
3.844
ASP351
2.713
GLU353
3.074
LEU354
3.783
TRP383
3.811
LEU384
4.431
LEU387
3.820
MET388
3.826
LEU391
3.484
Residue
Distance (Å)
ARG394
2.682
PHE404
3.480
MET421
4.116
ILE424
3.268
PHE425
4.412
LEU428
3.732
GLY521
4.350
HIS524
1.309
LEU525
3.527
ASN532
3.407
VAL533
3.605
VAL534
4.448
PRO535
3.586
References  Top
REF 1 Stereospecific lasofoxifene derivatives reveal the interplay between estrogen receptor alpha stability and antagonistic activity in ESR1 mutant breast cancer cells. Elife. 2022 May 16;11:e72512.
REF 2 Biochemical and Structural Basis for Constitutive Activity and Reduced SERM Potency in Acquired SERM/AI Resistant Metastatic Breast Cancers via ESR1 Somatic Mutation

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