Target Binding Site Detail

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Target General Information
Ligand General Information
Drug Binding Sites of Target
References
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
ABL1_HUMAN
Ligand General Information  Top
Ligand Name VX-680 Ligand Info
Canonical SMILES CC1=CC(=NN1)NC2=CC(=NC(=N2)SC3=CC=C(C=C3)NC(=O)C4CC4)N5CCN(CC5)C
InChI 1S/C23H28N8OS/c1-15-13-20(29-28-15)25-19-14-21(31-11-9-30(2)10-12-31)27-23(26-19)33-18-7-5-17(6-8-18)24-22(32)16-3-4-16/h5-8,13-14,16H,3-4,9-12H2,1-2H3,(H,24,32)(H2,25,26,27,28,29)
InChIKey GCIKSSRWRFVXBI-UHFFFAOYSA-N
PubChem Compound ID 5494449
Drug Binding Sites of Target  Top
PDB ID: 2F4J      Structure of the Kinase Domain of an Imatinib-Resistant Abl Mutant in Complex with the Aurora Kinase Inhibitor VX-680
Method X-ray diffraction Resolution 1.91 Å Mutation Yes [1]
PDB Sequence
GMSPNYDKWE
236
MERTDITMKH
246
KLGGGQYGEV
256
YEGVWKKYSL
266
TVAVKTLKED
276

TMEVEEFLKE
286
AAVMKEIKHP
296
NLVQLLGVCT
306
REPPFYIITE
316
FMTYGNLLDY
326

LRECNRQEVN
336
AVVLLYMATQ
346
ISSAMEYLEK
356
KNFIHRDLAA
366
RNCLVGENHL
376

VKVADFGLSR
386
LMTGDTYTAP
396
AGAKFPIKWT
406
APESLAYNKF
416
SIKSDVWAFG
426

VLLWEIATYG
436
MSPYPGIDLS
446
QVYELLEKDY
456
RMERPEGCPE
466
KVYELMRACW
476

QWNPSDRPSF
486
AEIHQAFETM
496
FQESSISDEV
506
EKELGKQ
Residue
Distance (Å)
LEU248
3.903
GLY249
3.660
TYR253
3.416
VAL256
3.462
ALA269
3.391
VAL270
4.941
LYS271
3.542
GLU286
3.633
MET290
4.038
VAL299
3.938
ILE313
3.823
Residue
Distance (Å)
THR315
3.042
GLU316
2.632
PHE317
3.320
MET318
2.729
THR319
3.235
TYR320
3.936
GLY321
3.503
ASN322
4.841
LEU370
3.398
ASP381
3.069
PDB ID: 4ZOG      VX-680/MK-0457 binds to human ABL1 also in inactive DFG conformations.
Method X-ray diffraction Resolution 2.30 Å Mutation No [2]
PDB Sequence
DKWEMERTDI
242
TMKHKLGGGQ
252
YGEVYEGVWK
262
KYSLTVAVKT
272
LKEDTMEVEE
282

FLKEAAVMKE
292
IKHPNLVQLL
302
GVCTREPPFY
312
IITEFMTYGN
322
LLDYLRECNR
332

QEVNAVVLLY
342
MATQISSAME
352
YLEKKNFIHR
362
DLAARNCLVG
372
ENHLVKVADF
382

GLSRLMTGDT
392
YTAHAGAKFP
402
IKWTAPESLA
412
YNKFSIKSDV
422
WAFGVLLWEI
432

ATYGMSPYPG
442
IDLSQVYELL
452
EKDYRMERPE
462
GCPEKVYELM
472
RACWQWNPSD
482

RPSFAEIHQA
492
FETMFQESS
Residue
Distance (Å)
LEU248
3.680
GLY249
4.125
TYR253
3.373
VAL256
3.594
ALA269
3.309
VAL270
4.818
LYS271
3.632
MET290
4.108
VAL299
4.303
ILE313
3.663
Residue
Distance (Å)
THR315
3.400
GLU316
2.831
PHE317
3.546
MET318
2.642
THR319
2.993
TYR320
3.498
GLY321
3.414
ASN322
4.918
LEU370
3.540
PHE382
3.772
References  Top
REF 1 Structure of the kinase domain of an imatinib-resistant Abl mutant in complex with the Aurora kinase inhibitor VX-680. Cancer Res. 2006 Jan 15;66(2):1007-14.
REF 2 VX-680/MK-0457 binds also to human ABL1 with inactive DFG conformations.

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