Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T98933 | Target Info | |||
| Target Name | Thyroid hormone receptor beta (THRB) | ||||
| Synonyms | c-erbA-beta; c-erbA-2; THR1; Nuclear receptor subfamily 1 group A member 2; NR1A2; ERBA2 | ||||
| Target Type | Successful Target | ||||
| Gene Name | THRB | ||||
| Biochemical Class | Nuclear hormone receptor | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | Tiratricol | Ligand Info | |||
| Canonical SMILES | C1=CC(=C(C=C1OC2=C(C=C(C=C2I)CC(=O)O)I)I)O | ||||
| InChI | 1S/C14H9I3O4/c15-9-6-8(1-2-12(9)18)21-14-10(16)3-7(4-11(14)17)5-13(19)20/h1-4,6,18H,5H2,(H,19,20) | ||||
| InChIKey | UOWZUVNAGUAEQC-UHFFFAOYSA-N | ||||
| PubChem Compound ID | 5803 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 3D57 TR Variant D355R | ||||||
| Method | X-ray diffraction | Resolution | 2.20 Å | Mutation | Yes | [1] |
| PDB Sequence |
HKPEPTDEEW
219 ELIKTVTEAH229 VATNAQGSHW239 KQKRKFLPED249 IGQAPGGKVD265 LEAFSHFTKI 275 ITPAITRVVD285 FAKKLPMFCE295 LPCEDQIILL305 KGCCMEIMSL315 RAAVRYDPES 325 ETLTLNGEMA335 VTRGQLKNGG345 LGVVSDAIFR355 LGMSLSSFNL365 DDTEVALLQA 375 VLLMSSDRPG385 LACVERIEKY395 QDSFLLAFEH405 YINYRKHHVT415 HFWPKLLMKV 425 TDLRMIGACH435 ASRFLHMKVE445 CPTELFPPLF455 LEVFE
|
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|
|
ASN233
4.917
PHE269
3.889
PHE272
3.397
ILE275
3.895
ILE276
3.718
ALA279
3.872
MET310
3.935
MET313
3.365
SER314
4.503
ARG316
3.721
ALA317
3.615
ARG320
2.945
THR329
3.966
|
|||||
| PDB ID: 1NQ2 Two RTH Mutants with Impaired Hormone Binding | ||||||
| Method | X-ray diffraction | Resolution | 2.40 Å | Mutation | Yes | [2] |
| PDB Sequence |
ASAAEELQKS
207 IGHKPEPTDE217 EWELIKTVTE227 AHVATNAQGS237 HWKQKRKFLP247 EDIGQAGKVD 265 LEAFSHFTKI275 ITPAITRVVD285 FAKKLPMFCE295 LPCEDQIILL305 KGCCMEIMSL 315 RTAVRYEPES325 ETLTLNGEMA335 VTRGQLKNGG345 LGVVSDAIFD355 LGMSLSSFNL 365 DDTEVALLQA375 VLLMSSDRPG385 LACVERIEKY395 QDSFLLAFEH405 YINYRKHHVT 415 HFWPKLLMKV425 TDLRMIGACH435 ASRFLHMKVE445 CPTELFPPLF455 LEVFE |
|||||
|
|
PHE269
4.031
PHE272
3.074
THR273
4.872
ILE275
3.834
ILE276
3.703
ALA279
3.521
ARG282
2.981
MET310
3.801
MET313
3.670
SER314
4.374
ARG316
3.906
THR317
3.289
|
|||||
| PDB ID: 1NQ0 TR Receptor Mutations Conferring Hormone Resistance and Reduced Corepressor Release Exhibit Decreased Stability in the Nterminal LBD | ||||||
| Method | X-ray diffraction | Resolution | 2.40 Å | Mutation | Yes | [3] |
| PDB Sequence |
AAMEELQKSI
208 GHKPEPTDEE218 WELIKTVTEA228 HVATNTQGSH238 WKQKRKFLPE248 DIGQKVDLEA 268 FSHFTKIITP278 AITRVVDFAK288 KLPMFCELPC298 EDQIILLKGC308 CMEIMSLRAA 318 VRYDPESETL328 TLNGEMAVTR338 GQLKNGGLGV348 VSDAIFDLGM358 SLSSFNLDDT 368 EVALLQAVLL378 MSSDRPGLAC388 VERIEKYQDS398 FLLAFEHYIN408 YRKHHVTHFW 418 PKLLMKVTDL428 RMIGACHASR438 FLHMKVECPT448 ELFPPLFLEV458 FED |
|||||
|
|
ASN233
4.801
PHE269
3.752
PHE272
3.329
THR273
4.675
ILE275
3.824
ILE276
3.767
ALA279
3.671
MET310
3.588
MET313
3.204
SER314
4.444
ARG316
3.807
ALA317
3.725
ARG320
2.925
|
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| PDB ID: 3JZC Crystal Structure of TR-beta bound to the selective thyromimetic TRIAC | ||||||
| Method | X-ray diffraction | Resolution | 2.50 Å | Mutation | No | [4] |
| PDB Sequence |
EELQKSIGHK
211 PEPTDEEWEL221 IKTVTEAHVA231 TNAQGSHWKQ241 KRKFLPEDIG251 QVDLEAFSHF 272 TKIITPAITR282 VVDFAKKLPM292 FELPEDQIIL304 LKGCCMEIMS314 LRAAVRYDPE 324 SETLTLNGEM334 AVTRGQLKNG344 GLGVVSDAIF354 DLGMSLSSFN364 LDDTEVALLQ 374 AVLLMSSDRP384 GLAVERIEKY395 QDSFLLAFEH405 YINYRKHHVT415 HFWPKLLMKV 425 TDLRMIGAHA436 SRFLHMKVEC446 PTELFPPLFL456 EVFE
|
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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 .4HY or .4HY2 or .4HY3 or :34HY;style chemicals stick;color identity;select .A:269 or .A:272 or .A:273 or .A:275 or .A:276 or .A:279 or .A:310 or .A:313 or .A:314 or .A:316 or .A:317 or .A:320 or .A:329 or .A:330 or .A:331 or .A:332 or .A:341 or .A:344 or .A:345 or .A:346 or .A:353 or .A:435 or .A:442 or .A:455; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
PHE269
4.065
PHE272
3.237
THR273
4.915
ILE275
3.800
ILE276
3.628
ALA279
3.603
MET310
3.909
MET313
3.158
SER314
4.395
ARG316
4.409
ALA317
3.932
ARG320
2.997
|
|||||
| PDB ID: 1NQ1 TR Receptor Mutations Conferring Hormone Resistance and Reduced Corepressor Release Exhibit Decreased Stability in the Nterminal LBD | ||||||
| Method | X-ray diffraction | Resolution | 2.90 Å | Mutation | Yes | [3] |
| PDB Sequence |
AAMEELQKSI
208 GHKPEPTDEE218 WELIKTVTEA228 HVATNAQGSH238 WKQKQKFLPD248 DIGQKVDLEA 268 FSHFTKIITP278 AITRVVDFAK288 KLPMFCELPC298 EDQIILLKGC308 CMEIMSLRAA 318 VRYDPESETL328 TLNGEMAVTR338 GQLKNGGLGV348 VSDAIFDLGM358 SLSSFNLDDT 368 EVALLQAVLL378 MSSDRPGLAC388 VERIEKYQDS398 FLLAFEHYIN408 YRKHHVTHFW 418 PKLLMKVTDL428 RMIGACHASR438 FLHMKVECPT448 ELFPPLFLEV458 FED |
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .4HY or .4HY2 or .4HY3 or :34HY;style chemicals stick;color identity;select .A:269 or .A:272 or .A:273 or .A:275 or .A:276 or .A:279 or .A:310 or .A:313 or .A:314 or .A:316 or .A:317 or .A:320 or .A:329 or .A:330 or .A:331 or .A:332 or .A:341 or .A:344 or .A:345 or .A:346 or .A:353 or .A:435 or .A:442 or .A:455; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
PHE269
4.078
PHE272
4.036
THR273
4.877
ILE275
4.207
ILE276
3.440
ALA279
3.819
MET310
4.067
MET313
3.165
SER314
4.561
ARG316
4.279
ALA317
3.577
ARG320
2.986
|
|||||
| PDB ID: 1NUO Two RTH Mutants with Impaired Hormone Binding | ||||||
| Method | X-ray diffraction | Resolution | 3.10 Å | Mutation | Yes | [2] |
| PDB Sequence |
MEELQKSIGH
210 KPEPTDEEWE220 LIKTVTEAHV230 ATNAGSHWKQ240 KRKFLPDDIG250 QDLEAFSHFT 273 KIITPAITRV283 VDFAKKLPMF293 CELPCEDQII303 LLKGCCMEIM313 SLHAAVRYDP 323 ESETLTLNGE333 MAVTRGQLKN343 GGLGVVSDAI353 FDLGMSLSSF363 NLDDTEVALL 373 QAVLLMSSDR383 PGLACVERIE393 KYQDSFLLAF403 EHYINYRKHH413 VTHFWPKLLM 423 KVTDLRMIGA433 CHASRFLHMK443 VECPTELFPP453 LFLEVFE
|
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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 .4HY or .4HY2 or .4HY3 or :34HY;style chemicals stick;color identity;select .A:269 or .A:272 or .A:275 or .A:276 or .A:279 or .A:310 or .A:313 or .A:314 or .A:316 or .A:317 or .A:320 or .A:330 or .A:331 or .A:341 or .A:344 or .A:345 or .A:346 or .A:353 or .A:435 or .A:442 or .A:455; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
PHE269
3.788
PHE272
3.691
ILE275
3.943
ILE276
2.578
ALA279
2.837
MET310
3.623
MET313
3.137
SER314
4.730
HIS316
3.311
ALA317
3.702
ARG320
4.038
|
|||||
| PDB ID: 2PIN Thyroid receptor beta in complex with inhibitor | ||||||
| Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | Yes | [5] |
| PDB Sequence |
HKPEPTDEEW
219 ELIKTVTEAH229 VATNAQGSHW239 KQKRKFLPED249 IGQAPGGKVD265 LEAFSHFTKI 275 ITPAITRVVD285 FAKKLPMFCE295 LPCEDQIILL305 KGCCMEIMSL315 RAAVRYDPES 325 ETLTLNGEMA335 VTRGQLKNGG345 LGVVSDAIFR355 LGMSLSSFNL365 DDTEVALLQA 375 VLLMSSDRPG385 LACVERIEKY395 QDSFLLAFEH405 YINYRKHHVT415 HFWPKLLMKV 425 TDLRMIGACH435 ASRFLHMKVE445 CPTELFPPLF455 LEVFE
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .4HY or .4HY2 or .4HY3 or :34HY;style chemicals stick;color identity;select .A:233 or .A:269 or .A:272 or .A:273 or .A:275 or .A:276 or .A:279 or .A:310 or .A:313 or .A:314 or .A:316 or .A:317 or .A:320 or .A:329 or .A:330 or .A:331 or .A:332 or .A:341 or .A:344 or .A:345 or .A:346 or .A:353 or .A:435 or .A:442 or .A:455; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
ASN233
4.919
PHE269
3.773
PHE272
3.329
THR273
4.938
ILE275
3.896
ILE276
3.724
ALA279
3.831
MET310
3.960
MET313
3.463
SER314
4.552
ARG316
3.975
ALA317
3.391
ARG320
2.847
|
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Molecular basis for dimer formation of TRbeta variant D355R. Proteins. 2009 Apr;75(1):111-7. | ||||
| REF 2 | Two resistance to thyroid hormone mutants with impaired hormone binding. Mol Endocrinol. 2003 Apr;17(4):643-52. | ||||
| REF 3 | Thyroid hormone receptor-beta mutations conferring hormone resistance and reduced corepressor release exhibit decreased stability in the N-terminal ligand-binding domain. Mol Endocrinol. 2003 Jan;17(1):107-16. | ||||
| REF 4 | Gaining ligand selectivity in thyroid hormone receptors via entropy. Proc Natl Acad Sci U S A. 2009 Dec 8;106(49):20717-22. | ||||
| REF 5 | Structural insight into the mode of action of a direct inhibitor of coregulator binding to the thyroid hormone receptor. Mol Endocrinol. 2007 Dec;21(12):2919-28. | ||||
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