Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T49989 | Target Info | |||
| Target Name | TGF-beta receptor type II (TGFBR2) | ||||
| Synonyms | Transforminggrowth factor-beta receptor type II; Transforming growth factor-beta receptor type II; TbetaR-II; TGFR-2; TGF-beta type II receptor; TGF-beta receptor type-2 | ||||
| Target Type | Clinical trial Target | ||||
| Gene Name | TGFBR2 | ||||
| Biochemical Class | Kinase | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: Staurosporine | Ligand Info | |||||
| Structure Description | TGF-BETA RECEPTOR TYPE 2 KINASE DOMAIN (E431A,R433A,E485A,K488A,R493A,R495A) IN COMPLEX WITH STAUROSPORINE | PDB:5E8Y | ||||
| Method | X-ray diffraction | Resolution | 2.05 Å | Mutation | Yes | [1] |
| PDB Sequence |
ELLPIELDTL
249 VGKGRFAEVY259 KAKLKQQFET273 VAVKIFPYEE283 YASWKTEKDI293 FSDINLKHEN 303 ILQFLTAEER313 KTELGKQYWL323 ITAFHAKGNL333 QEYLTRHVIS343 WEDLRKLGSS 353 LARGIAHLHS363 DHTPCGRPKM373 PIVHRDLKSS383 NILVKNDLTC393 CLCDFGLSLR 403 LDPTLSVDDL413 ANSGQVGTAR423 YMAPEVLASA433 MNLENVESFK443 QTDVYSMALV 453 LWEMTSRCNA463 VGEVKDYEPP473 FGSKVREHPC483 VASMADNVLA493 DAGRPEIPSF 503 WLNHQGIQMV513 CETLTECWDH523 DPEARLTAQC533 VAERFSEL
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VAL250
2.175
GLY251
2.945
LYS252
2.849
GLY253
3.725
ALA256
4.647
VAL258
2.887
ALA275
3.192
LYS277
2.469
GLU290
3.793
LEU305
2.863
THR325
3.006
ALA326
2.074
PHE327
3.030
|
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| Ligand Name: AMP-PNP | Ligand Info | |||||
| Structure Description | TGF-BETA RECEPTOR TYPE 2 KINASE DOMAIN (E431A,R433A,E485A,K488A,R493A,R495A) IN COMPLEX WITH AMPPNP | PDB:5E92 | ||||
| Method | X-ray diffraction | Resolution | 2.08 Å | Mutation | Yes | [1] |
| PDB Sequence |
ELLPIELDTL
249 VGKGRFAEVY259 KAKLKFETVA275 VKIFPYEEYA285 SWKTEKDIFS295 DINLKHENIL 305 QFLTAEERKT315 ELGKQYWLIT325 AFHAKGNLQE335 YLTRHVISWE345 DLRKLGSSLA 355 RGIAHLHSDH365 TPCGRPKMPI375 VHRDLKSSNI385 LVKNDLTCCL395 CDFGLSLRLD 405 PTLSVDDLAN415 SGQVGTARYM425 APEVLASAMN435 LENVESFKQT445 DVYSMALVLW 455 EMTSRCNAVG465 EVKDYEPPFG475 SKVREHPCVA485 SMADNVLADA495 GRPEIPSFWL 505 NHQGIQMVCE515 TLTECWDHDP525 EARLTAQCVA535 ERFSELEH
|
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VAL250
3.767
GLY251
2.998
LYS252
3.354
GLY253
3.044
ARG254
2.996
PHE255
3.131
ALA256
3.118
VAL258
3.460
ALA275
3.454
LYS277
2.791
PHE279
4.770
SER286
4.515
GLU290
3.621
LEU305
3.057
THR325
2.875
|
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| Ligand Name: 5-[(3S)-5,5-dimethyloxolan-3-yl]-6-methoxy-3-(2-methoxypyridin-4-yl)pyrazolo[1,5-a]pyrimidine | Ligand Info | |||||
| Structure Description | Discovery of Functionally Selective Transforming Growth Factor beta Type II Receptor (TGF-beta RII) Inhibitors as Anti-Fibrosis Agents | PDB:7DV6 | ||||
| Method | X-ray diffraction | Resolution | 2.39 Å | Mutation | Yes | [2] |
| PDB Sequence |
ELLPIELDTL
249 VGKGRFAEVY259 KAKLKQNTSE269 QFETVAVKIF279 PYEEYASWKT289 EKDIFSDINL 299 KHENILQFLT309 AEERKTELGK319 QYWLITAFHA329 KGNLQEYLTR339 HVISWEDLRK 349 LGSSLARGIA359 HLHSDHTPCG369 RPKMPIVHRD379 LKSSNILVKN389 DLTCCLCDFG 399 LSLRLDPTLS409 VDDLANSGQV419 GTARYMAPEV429 LASAMNLENV439 ESFKQTDVYS 449 MALVLWEMTS459 RCNAVGEVKD469 YEPPFGSKVR479 EHPCVASMAD489 NVLADAGRPE 499 IPSFWLNHQG509 IQMVCETLTE519 CWDHDPEARL529 TAQCVAERFS539 ELEH |
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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 .HJF or .HJF2 or .HJF3 or :3HJF;style chemicals stick;color identity;select .A:250 or .A:251 or .A:258 or .A:275 or .A:277 or .A:305 or .A:325 or .A:326 or .A:327 or .A:328 or .A:329 or .A:330 or .A:331 or .A:332 or .A:383 or .A:384 or .A:386 or .A:396 or .A:397; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: N-{4-[3-(6-methoxypyridin-3-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}acetamide | Ligand Info | |||||
| Structure Description | TGF-BETA RECEPTOR TYPE 2 KINASE DOMAIN IN COMPLEX WITH N- {4-[3-(6-METHOXYPYRIDIN-3-YL)-1H-PYRROLO[3,2-B]PYRIDIN-2- YL]PYRIDIN-2-YL}ACETAMIDE | PDB:5QIN | ||||
| Method | X-ray diffraction | Resolution | 1.57 Å | Mutation | Yes | [3] |
| PDB Sequence |
ELLPIELDTL
249 VGKGRFAEVY259 KAKLKQFETV274 AVKIFPYEEY284 ASWKTEKDIF294 SDINLKHENI 304 LQFLTAEERK314 TELGKQYWLI324 TAFHAKGNLQ334 EYLTRHVISW344 EDLRKLGSSL 354 ARGIAHLHSD364 HTPCGRPKMP374 IVHRDLKSSN384 ILVKNDLTCC394 LCDFGLSLRL 404 DPTLSVDDLA414 NQVGTARYMA426 PEVLASAMNL436 ENVESFKQTD446 VYSMALVLWE 456 MTSRCNAVGE466 VKDYEPPFGS476 KVREHPCVAS486 MADNVLADAG496 RPEIPSFWLN 506 HQGIQMVCET516 LTECWDHDPE526 ARLTAQCVAE536 RFSEL
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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 .J2V or .J2V2 or .J2V3 or :3J2V;style chemicals stick;color identity;select .A:250 or .A:252 or .A:253 or .A:254 or .A:258 or .A:275 or .A:276 or .A:277 or .A:290 or .A:294 or .A:305 or .A:307 or .A:323 or .A:324 or .A:325 or .A:326 or .A:327 or .A:328 or .A:329 or .A:330 or .A:331 or .A:332 or .A:383 or .A:384 or .A:386 or .A:396 or .A:397; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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VAL250
3.574
LYS252
3.900
GLY253
3.561
ARG254
4.821
VAL258
2.875
ALA275
3.092
VAL276
3.993
LYS277
2.871
GLU290
3.627
PHE294
2.754
LEU305
3.093
PHE307
3.735
LEU323
2.890
ILE324
4.543
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| Ligand Name: 3-Amino-6-[4-(2-Hydroxyethyl)phenyl]-N-[4-(Morpholin-4-Yl)pyridin-3-Yl]pyrazine-2-Carboxamide | Ligand Info | |||||
| Structure Description | TGF-BETA RECEPTOR TYPE 2 KINASE DOMAIN (E431A,R433A,E485A,K488A,R493A,R495A) IN COMPLEX WITH 3-AMINO-6-[4-(2- HYDROXYETHYL)PHENYL]-N-[4-(MORPHOLIN-4-YL)PYRIDIN-3-YL] PYRAZINE-2-CARBOXAMIDE | PDB:5E91 | ||||
| Method | X-ray diffraction | Resolution | 2.42 Å | Mutation | Yes | [1] |
| PDB Sequence |
ELLPIELDTL
249 VGKGRFAEVY259 KAKLKETVAV276 KIFPYEEYAS286 WKTEKDIFSD296 INLKHENILQ 306 FLTAEERKTE316 LGKQYWLITA326 FHAKGNLQEY336 LTRHVISWED346 LRKLGSSLAR 356 GIAHLHSDHT366 PCGRPKMPIV376 HRDLKSSNIL386 VKNDLTCCLC396 DFGLSLRLDP 406 TLSVDDLANS416 GQVGTARYMA426 PEVLASAMNL436 ENVESFKQTD446 VYSMALVLWE 456 MTSRCNAVGE466 VKDYEPPFGS476 KVREHPCVAS486 MADNVLADAG496 RPEIPSFWLN 506 HQGIQMVCET516 LTECWDHDPE526 ARLTAQCVAE536 RFSELEH
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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 .5L4 or .5L42 or .5L43 or :35L4;style chemicals stick;color identity;select .A:249 or .A:250 or .A:251 or .A:252 or .A:253 or .A:258 or .A:275 or .A:277 or .A:305 or .A:325 or .A:326 or .A:327 or .A:328 or .A:329 or .A:330 or .A:331 or .A:332 or .A:383 or .A:384 or .A:385 or .A:386 or .A:396 or .A:397; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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LEU249
4.992
VAL250
2.603
GLY251
3.319
LYS252
3.459
GLY253
3.872
VAL258
3.644
ALA275
3.476
LYS277
2.819
LEU305
2.861
THR325
3.199
ALA326
1.868
PHE327
2.808
|
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| Ligand Name: 3-[2-(2-Hydroxyethyl)pyridinium-1-Yl]propane-1-Sulfonate | Ligand Info | |||||
| Structure Description | Extracellular domain of type II Transforming Growth Factor Beta receptor in complex with 2-(2-Hydroxyethyl)NDSB-201 | PDB:4XJJ | ||||
| Method | X-ray diffraction | Resolution | 1.40 Å | Mutation | Yes | [4] |
| PDB Sequence |
ALCKFCDVRF
35 STCDNQKSCM45 SNCSITSICE55 KPQEVCVAVW65 RKNDENITLE75 TVCHDPKLPY 85 HDFILEDAAS95 PTCIMKEKKK105 PGETFFMCSC115 SSDECNDNII125 FSEEY |
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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 .41D or .41D2 or .41D3 or :341D;style chemicals stick;color identity;select .A:38 or .A:39 or .A:40 or .A:41 or .A:44 or .A:65 or .A:67 or .A:111 or .A:126; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 3-(Pyridin-1-ium-1-yl)propane-1-sulfonate | Ligand Info | |||||
| Structure Description | Extracellular domain of type II Transforming Growth Factor Beta receptor in complex with NDSB-201 | PDB:4P7U | ||||
| Method | X-ray diffraction | Resolution | 1.50 Å | Mutation | Yes | [5] |
| PDB Sequence |
ALCKFCDVRF
35 STCDNQKSCM45 SNCSITSICE55 KPQEVCVAVW65 RKNDENITLE75 TVCHDPKLPY 85 HDFILEDAAS95 PTCIMKEKKK105 PGETFFMCSC115 SSDECNDNII125 FS |
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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 .1PS or .1PS2 or .1PS3 or :31PS;style chemicals stick;color identity;select .A:38 or .A:39 or .A:40 or .A:41 or .A:44 or .A:65 or .A:67 or .A:109 or .A:111 or .A:126; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Crystal structures of apo and inhibitor-bound TGFbetaR2 kinase domain: insights into TGFbetaR isoform selectivity. Acta Crystallogr D Struct Biol. 2016 May;72(Pt 5):658-74. | ||||
| REF 2 | Discovery of Selective Transforming Growth Factor beta Type II Receptor Inhibitors as Antifibrosis Agents. ACS Med Chem Lett. 2021 Apr 21;12(5):745-751. | ||||
| REF 3 | Discovery of 4-Azaindole Inhibitors of TGFbetaRI as Immuno-oncology Agents. ACS Med Chem Lett. 2018 Oct 17;9(11):1117-1122. | ||||
| REF 4 | Extracellular domain of type II Transforming Growth Factor Beta receptor in complex with 2-(2-Hydroxyethyl)NDSB-201 | ||||
| REF 5 | The non-detergent sulfobetaine-201 acts as a pharmacological chaperone to promote folding and crystallization of the type II TGF-beta receptor extracellular domain. Protein Expr Purif. 2015 Nov;115:19-25. | ||||
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