Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T00348 | Target Info | |||
| Target Name | ABL T315I mutant (ABL T315I) | ||||
| Synonyms | p150 T315I; T315I Abl; Proto-oncogene tyrosine-protein kinase ABL1 T315I; Proto-oncogene c-Abl T315I; JTK7 T315I; C-ABL T315I; Abl T315I; Abelson tyrosine-protein kinase 1 T315I; Abelson murine leukemia viral oncogene homolog 1 T315I | ||||
| Target Type | Patented-recorded Target | ||||
| Gene Name | ABL1 | ||||
| Biochemical Class | Kinase | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: Axitinib | Ligand Info | |||||
| Structure Description | The crystal structure of human abl1 T315I gatekeeper mutant kinase domain in complex with axitinib | PDB:4TWP | ||||
| Method | X-ray diffraction | Resolution | 2.40 Å | Mutation | Yes | [1] |
| PDB Sequence |
DKWEMERTDI
242 TMKHKLGGGQ252 YGEVYEGVWK262 KYSLTVAVKT272 LEVEEFLKEA287 AVMKEIKHPN 297 LVQLLGVCTR307 EPPFYIIIEF317 MTYGNLLDYL327 RECNRQEVNA337 VVLLYMATQI 347 SSAMEYLEKK357 NFIHRDLAAR367 NCLVGENHLV377 KVADFGLSRL387 MTGDTYTAHA 397 GAKFPIKWTA407 PESLAYNKFS417 IKSDVWAFGV427 LLWEIATYGM437 SPYPGIDLSQ 447 VYELLEKDYR457 MERPEGCPEK467 VYELMRACWQ477 WNPSDRPSFA487 EIHQAFETMF 497 QESSIS
|
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|
|
LEU248
3.616
GLY249
4.119
TYR253
2.880
VAL256
3.926
ALA269
3.644
LYS271
2.688
GLU286
4.062
VAL299
4.712
ILE315
4.301
GLU316
2.720
PHE317
3.332
|
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| Ligand Name: PHA-739358 | Ligand Info | |||||
| Structure Description | Crystal structure of the T315I Abl mutant in complex with the inhibitor PHA-739358 | PDB:2V7A | ||||
| Method | X-ray diffraction | Resolution | 2.50 Å | Mutation | Yes | [2] |
| PDB Sequence |
DKWEMERTDI
242 TMKHKLGGGQ252 YGEVYEGVWK262 KYSLTVAVKT272 LKEDTMEVEE282 FLKEAAVMKE 292 IKHPNLVQLL302 GVCTREPPFY312 IIIEFMTYGN322 LLDYLRECNR332 QEVNAVVLLY 342 MATQISSAME352 YLEKKNFIHR362 DLAARNCLVG372 ENHLVKVADF382 GLSRLMTGDT 392 TAHAGAKFPI403 KWTAPESLAY413 NKFSIKSDVW423 AFGVLLWEIA433 TYGMSPYPGI 443 DLSQVYELLE453 KDYRMERPEG463 CPEKVYELMR473 ACWQWNPSDR483 PSFAEIHQAF 493 ETMFQESSIS503
|
|||||
|
|
LEU248
3.388
GLY250
3.174
GLY251
4.300
GLN252
4.946
VAL256
4.203
ALA269
3.405
LYS271
2.994
GLU286
4.523
VAL299
4.382
ILE315
4.125
GLU316
2.826
PHE317
3.681
|
|||||
| Ligand Name: DCC-2036 | Ligand Info | |||||
| Structure Description | The crystal structure of human abl1 kinase domain T315I mutant in complex with DCC-2036 | PDB:3QRJ | ||||
| Method | X-ray diffraction | Resolution | 1.82 Å | Mutation | Yes | [3] |
| PDB Sequence |
KWEMERTDIT
243 MKHKLGGGQY253 GEVYEGVWKK263 YSLTVAVKTL273 EVEEFLKEAA288 VMKEIKHPNL 298 VQLLGVCTRE308 PPFYIIIEFM318 TYGNLLDYLR328 ECNRQEVNAV338 VLLYMATQIS 348 SAMEYLEKKN358 FIHRDLAARN368 CLVGENHLVK378 VADFGLSRLM388 TGDTYTAHAG 398 AKFPIKWTAP408 ESLAYNKFSI418 KSDVWAFGVL428 LWEIATYGMS438 PYPGIDLSQV 448 YELLEKDYRM458 ERPEGCPEKV468 YELMRACWQW478 NPSDRPSFAE488 IHQAFETM |
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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 .919 or .9192 or .9193 or :3919;style chemicals stick;color identity;select .A:248 or .A:249 or .A:256 or .A:269 or .A:271 or .A:282 or .A:285 or .A:286 or .A:289 or .A:290 or .A:293 or .A:298 or .A:299 or .A:313 or .A:315 or .A:316 or .A:317 or .A:318 or .A:319 or .A:320 or .A:321 or .A:354 or .A:359 or .A:361 or .A:370 or .A:379 or .A:380 or .A:381 or .A:382 or .A:383; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LEU248
3.323
GLY249
4.930
VAL256
3.312
ALA269
3.165
LYS271
3.324
GLU282
3.579
LYS285
4.949
GLU286
2.936
VAL289
4.280
MET290
3.574
ILE293
3.752
LEU298
3.934
VAL299
3.460
ILE313
4.453
ILE315
3.276
|
|||||
| Ligand Name: Phosphonotyrosine | Ligand Info | |||||
| Structure Description | Crystal structure of the T315I Abl mutant in complex with the inhibitor PHA-739358 | PDB:2V7A | ||||
| Method | X-ray diffraction | Resolution | 2.50 Å | Mutation | Yes | [2] |
| PDB Sequence |
DKWEMERTDI
242 TMKHKLGGGQ252 YGEVYEGVWK262 KYSLTVAVKT272 LKEDTMEVEE282 FLKEAAVMKE 292 IKHPNLVQLL302 GVCTREPPFY312 IIIEFMTYGN322 LLDYLRECNR332 QEVNAVVLLY 342 MATQISSAME352 YLEKKNFIHR362 DLAARNCLVG372 ENHLVKVADF382 GLSRLMTGDT 392 TAHAGAKFPI403 KWTAPESLAY413 NKFSIKSDVW423 AFGVLLWEIA433 TYGMSPYPGI 443 DLSQVYELLE453 KDYRMERPEG463 CPEKVYELMR473 ACWQWNPSDR483 PSFAEIHQAF 493 ETMFQESSIS503
|
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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 .PTR or .PTR2 or .PTR3 or :3PTR;style chemicals stick;color identity;select .A:360 or .A:362 or .A:386 or .A:388 or .A:391 or .A:392 or .A:394 or .A:395 or .A:396 or .A:414 or .A:415 or .A:416 or .A:417; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Axitinib effectively inhibits BCR-ABL1(T315I) with a distinct binding conformation. Nature. 2015 Mar 5;519(7541):102-5. | ||||
| REF 2 | Crystal structure of the T315I Abl mutant in complex with the aurora kinases inhibitor PHA-739358. Cancer Res. 2007 Sep 1;67(17):7987-90. | ||||
| REF 3 | Conformational control inhibition of the BCR-ABL1 tyrosine kinase, including the gatekeeper T315I mutant, by the switch-control inhibitor DCC-2036. Cancer Cell. 2011 Apr 12;19(4):556-68. | ||||
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