Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T63505 | Target Info | |||
| Target Name | Tyrosine-protein kinase ABL1 (ABL) | ||||
| Synonyms | p150; Proto-oncogene tyrosine-protein kinase ABL1; Proto-oncogene c-Abl; JTK7; C-ABL; Abl; Abelson tyrosine-protein kinase 1; Abelson murine leukemia viral oncogene homolog 1 | ||||
| Target Type | Successful Target | ||||
| Gene Name | ABL1 | ||||
| Biochemical Class | Kinase | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | Imatinib | Ligand Info | |||
| Canonical SMILES | CC1=C(C=C(C=C1)NC(=O)C2=CC=C(C=C2)CN3CCN(CC3)C)NC4=NC=CC(=N4)C5=CN=CC=C5 | ||||
| InChI | 1S/C29H31N7O/c1-21-5-10-25(18-27(21)34-29-31-13-11-26(33-29)24-4-3-12-30-19-24)32-28(37)23-8-6-22(7-9-23)20-36-16-14-35(2)15-17-36/h3-13,18-19H,14-17,20H2,1-2H3,(H,32,37)(H,31,33,34) | ||||
| InChIKey | KTUFNOKKBVMGRW-UHFFFAOYSA-N | ||||
| PubChem Compound ID | 5291 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 3PYY Discovery and Characterization of a Cell-Permeable, Small-molecule c-Abl Kinase Activator that Binds to the Myristoyl Binding Site | ||||||
| Method | X-ray diffraction | Resolution | 1.85 Å | Mutation | No | [1] |
| PDB Sequence |
YDKWEMERTD
260 ITMKHKLGGG270 QYGEVYEGVW280 KKYSLTVAVK290 TLKEVEEFLK304 EAAVMKEIKH 314 PNLVQLLGVC324 TREPPFYIIT334 EFMTYGNLLD344 YLRECNRQEV354 NAVVLLYMAT 364 QISSAMEYLE374 KKNFIHRDLA384 ARNCLVGENH394 LVKVADFGLS404 RLMTGDTYTA 414 HAGAKFPIKW424 TAPESLAYNK434 FSIKSDVWAF444 GVLLWEIATY454 GMSPYPGIDL 464 SQVYELLEKD474 YRMERPEGCP484 EKVYELMRAC494 WQWNPSDRPS504 FAEIHQAFET 514 MFQES
|
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|
|
LEU267
3.758
TYR272
3.815
VAL275
3.855
ALA288
3.508
VAL289
4.125
LYS290
3.642
GLU305
2.942
VAL308
3.876
MET309
3.439
ILE312
3.655
VAL318
3.110
ILE332
3.752
THR334
2.978
GLU335
4.418
|
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| PDB ID: 6NPV C-abl Kinase domain with the activator(cmpd51), N-(1-(3,4-dichlorophenyl)-4-(2-hydroxyethyl)-4,5-dihydro-1H-pyrazol-3-yl)isonicotinamide | ||||||
| Method | X-ray diffraction | Resolution | 1.86 Å | Mutation | No | [2] |
| PDB Sequence |
YDKWEMERTD
260 ITMKHKLGGG270 QYGEVYEGVW280 KKYSLTVAVK290 TLKVEEFLKE305 AAVMKEIKHP 315 NLVQLLGVCT325 REPPFYIITE335 FMTYGNLLDY345 LRECNRQEVN355 AVVLLYMATQ 365 ISSAMEYLEK375 KNFIHRDLAA385 RNCLVGENHL395 VKVADFGLSR405 LMTGDTYTAH 415 AGAKFPIKWT425 APESLAYNKF435 SIKSDVWAFG445 VLLWEIATYG455 MSPYPGIDLS 465 QVYELLEKDY475 RMERPEGCPE485 KVYELMRACW495 QWNPSDRPSF505 AEIHQAFETM 515 FQES
|
|||||
|
|
LEU267
3.526
TYR272
3.787
VAL275
3.846
ALA288
3.524
VAL289
4.053
LYS290
3.571
GLU305
2.947
VAL308
3.848
MET309
3.304
ILE312
3.669
VAL318
3.217
ILE332
3.772
THR334
3.091
|
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| PDB ID: 6NPE C-abl Kinase domain with the activator(cmpd6), 2-cyano-N-(4-(3,4-dichlorophenyl)thiazol-2-yl)acetamide | ||||||
| Method | X-ray diffraction | Resolution | 2.15 Å | Mutation | No | [2] |
| PDB Sequence |
YDKWEMERTD
260 ITMKHKLGGG270 QYGEVYEGVW280 KKYSLTVAVK290 TLKVEEFLKE305 AAVMKEIKHP 315 NLVQLLGVCT325 REPPFYIITE335 FMTYGNLLDY345 LRECNRQEVN355 AVVLLYMATQ 365 ISSAMEYLEK375 KNFIHRDLAA385 RNCLVGENHL395 VKVADFGLSR405 LMTGDTYTAH 415 AGAKFPIKWT425 APESLAYNKF435 SIKSDVWAFG445 VLLWEIATYG455 MSPYPGIDLS 465 QVYELLEKDY475 RMERPEGCPE485 KVYELMRACW495 QWNPSDRPSF505 AEIHQAFETM 515 FQES
|
|||||
|
|
LEU267
3.497
TYR272
3.776
VAL275
4.002
ALA288
3.596
VAL289
4.133
LYS290
3.680
GLU305
2.824
VAL308
3.772
MET309
3.472
ILE312
3.652
VAL318
3.186
ILE332
3.622
THR334
3.093
|
|||||
| PDB ID: 6NPU C-abl Kinase domain with the activator(cmpd29), N-(1-(3,4-dichlorophenyl)-4,5-dihydro-1H-pyrazol-3-yl)acetamide | ||||||
| Method | X-ray diffraction | Resolution | 2.33 Å | Mutation | No | [2] |
| PDB Sequence |
YDKWEMERTD
260 ITMKHKLGGG270 QYGEVYEGVW280 KKYSLTVAVK290 TLKVEEFLKE305 AAVMKEIKHP 315 NLVQLLGVCT325 REPPFYIITE335 FMTYGNLLDY345 LRECNRQEVN355 AVVLLYMATQ 365 ISSAMEYLEK375 KNFIHRDLAA385 RNCLVGENHL395 VKVADFGLSR405 LMTGDTYTAH 415 AGAKFPIKWT425 APESLAYNKF435 SIKSDVWAFG445 VLLWEIATYG455 MSPYPGIDLS 465 QVYELLEKDY475 RMERPEGCPE485 KVYELMRACW495 QWNPSDRPSF505 AEIHQAFETM 515 FQES
|
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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 .STI or .STI2 or .STI3 or :3STI;style chemicals stick;color identity;select .A:267 or .A:272 or .A:275 or .A:288 or .A:289 or .A:290 or .A:305 or .A:308 or .A:309 or .A:312 or .A:317 or .A:318 or .A:332 or .A:334 or .A:335 or .A:336 or .A:337 or .A:340 or .A:373 or .A:378 or .A:379 or .A:380 or .A:381 or .A:389 or .A:398 or .A:399 or .A:400 or .A:401; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LEU267
3.377
TYR272
3.738
VAL275
3.846
ALA288
3.592
VAL289
3.932
LYS290
3.653
GLU305
2.872
VAL308
3.762
MET309
3.331
ILE312
3.892
LEU317
4.894
VAL318
3.177
ILE332
3.667
THR334
3.019
|
|||||
| PDB ID: 2HYY Human Abl kinase domain in complex with imatinib (STI571, Glivec) | ||||||
| Method | X-ray diffraction | Resolution | 2.40 Å | Mutation | No | [3] |
| PDB Sequence |
WEMERTDITM
244 KHKLGGGQYG254 EVYEGVWKKY264 SLTVAVKTLK274 DTMEVEEFLK285 EAAVMKEIKH 295 PNLVQLLGVC305 TREPPFYIIT315 EFMTYGNLLD325 YLRECNRQEV335 NAVVLLYMAT 345 QISSAMEYLE355 KKNFIHRDLA365 ARNCLVGENH375 LVKVADFGLS385 RLMTGDTYTA 395 HAGAKFPIKW405 TAPESLAYNK415 FSIKSDVWAF425 GVLLWEIATY435 GMSPYPGIDL 445 SQVYELLEKD455 YRMERPEGCP465 EKVYELMRAC475 WQWNPSDRPS485 FAEIHQAFET 495 MFQ
|
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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 .STI or .STI2 or .STI3 or :3STI;style chemicals stick;color identity;select .A:248 or .A:253 or .A:256 or .A:269 or .A:270 or .A:271 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:321 or .A:359 or .A:360 or .A:361 or .A:362 or .A:370 or .A:380 or .A:381 or .A:382; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LEU248
3.632
TYR253
3.658
VAL256
3.588
ALA269
3.437
VAL270
3.985
LYS271
3.583
GLU286
3.089
VAL289
3.773
MET290
3.255
ILE293
3.801
LEU298
4.675
VAL299
3.278
ILE313
3.832
|
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| PDB ID: 7N9G Crystal structure of the Abl 1b Kinase domain in complex with Dasatinib and Imatinib | ||||||
| Method | X-ray diffraction | Resolution | 2.20 Å | Mutation | No | [4] |
| PDB Sequence |
DKWEMERTDI
261 TMKHKLGGGQ271 YGEVYEGVWK281 KYSLTVAVKT291 LKMEVEEFLK304 EAAVMKEIKH 314 PNLVQLLGVC324 TREPPFYIIT334 EFMTYGNLLD344 YLRECNRQEV354 NAVVLLYMAT 364 QISSAMEYLE374 KKNFIHRDLA384 ARNCLVGENH394 LVKVADFGLS404 RLFPIKWTAP 427 ESLAYNKFSI437 KSDVWAFGVL447 LWEIATYGMS457 PYPGIDLSQV467 YELLEKDYRM 477 ERPEGCPEKV487 YELMRACWQW497 NPSDRPSFAE507 IHQAFETMFQ517 |
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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 .STI or .STI2 or .STI3 or :3STI;style chemicals stick;color identity;select .A:356 or .A:357 or .A:359 or .A:360 or .A:448 or .A:452 or .A:454 or .A:481 or .A:482 or .A:483 or .A:484 or .A:487 or .A:512 or .A:515 or .A:516 or .A:517; 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 | Discovery and characterization of a cell-permeable, small-molecule c-Abl kinase activator that binds to the myristoyl binding site. Chem Biol. 2011 Feb 25;18(2):177-86. | ||||
| REF 2 | Identification and Optimization of Novel Small c-Abl Kinase Activators Using Fragment and HTS Methodologies. J Med Chem. 2019 Feb 28;62(4):2154-2171. | ||||
| REF 3 | Structural biology contributions to the discovery of drugs to treat chronic myelogenous leukaemia. Acta Crystallogr D Biol Crystallogr. 2007 Jan;63(Pt 1):80-93. | ||||
| REF 4 | Imatinib can act as an Allosteric Activator of Abl Kinase. J Mol Biol. 2022 Jan 30;434(2):167349. | ||||
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