Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T99089 | Target Info | |||
| Target Name | Serine/threonine-protein kinase B-raf (BRAF) | ||||
| Synonyms | V-Raf murine sarcoma viral oncogene homolog B1; RAFB1; Proto-oncogene B-Raf; P94; BRAF1; BRAF(V599E); BRAF serine/threonine kinase; B-raf protein; B-Raf | ||||
| Target Type | Successful Target | ||||
| Gene Name | BRAF | ||||
| Biochemical Class | Kinase | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | AMP-PNP | Ligand Info | |||
| Canonical SMILES | C1=NC(=C2C(=N1)N(C=N2)C3C(C(C(O3)COP(=O)(O)OP(=O)(NP(=O)(O)O)O)O)O)N | ||||
| InChI | 1S/C10H17N6O12P3/c11-8-5-9(13-2-12-8)16(3-14-5)10-7(18)6(17)4(27-10)1-26-31(24,25)28-30(22,23)15-29(19,20)21/h2-4,6-7,10,17-18H,1H2,(H,24,25)(H2,11,12,13)(H4,15,19,20,21,22,23)/t4-,6-,7-,10-/m1/s1 | ||||
| InChIKey | PVKSNHVPLWYQGJ-KQYNXXCUSA-N | ||||
| PubChem Compound ID | 33113 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 7M0X Crystal structure of the BRAF:MEK1 kinases in complex with AMPPNP and PD0325901 | ||||||
| Method | X-ray diffraction | Resolution | 2.47 Å | Mutation | Yes | [1] |
| PDB Sequence |
SDDWEIPDGQ
456 ITVGQRIGSG466 SFGTVYKGKW476 HGDVAVKMLN486 VTAPTPQQLQ496 AFKNEVGVLR 506 KTRHVNILLF516 MGYSTKPQLA526 IVTQWCEGSS536 LYHHLHIIET546 KFEMIKLIDI 556 ARQTAQGMDY566 LHAKSIIHRD576 LKSNNIFLHE586 DLTVKIGDFG596 LATVKSRWSG 606 SHQFEQLSGS616 ILWMAPEVIR626 MQDKNPYSFQ636 SDVYAFGIVL646 YELMTGQLPY 656 SNINNRDQII666 FMVGRGYLSP676 DLSKVRSNCP686 KAMKRLMAEC696 LKKKRDERPL 706 FPQILASIEL716 LARSLP
|
|||||
|
|
ILE463
3.511
GLY464
3.657
SER465
3.736
GLY466
3.117
SER467
2.641
PHE468
3.797
GLY469
3.616
THR470
4.998
VAL471
3.482
ALA481
3.541
LYS483
2.784
LEU514
3.535
|
|||||
| PDB ID: 6PP9 Crystal structure of BRAF:MEK1 complex | ||||||
| Method | X-ray diffraction | Resolution | 2.59 Å | Mutation | Yes | [2] |
| PDB Sequence |
SDDWEIPDGQ
456 ITVGQRIGSG466 SFGTVYKGKW476 HGDVAVKMLN486 VTAPTPQQLQ496 AFKNEVGVLR 506 KTRHVNILLF516 MGYSTKPQLA526 IVTQWCEGSS536 LYHHLHIIET546 KFEMIKLIDI 556 ARQTAQGMDY566 LHAKSIIHRD576 LKSNNIFLHE586 DLTVKIGDFG596 LATVKSRWSG 606 SHQFEQLSGS616 ILWMAPEVIR626 MQDKNPYSFQ636 SDVYAFGIVL646 YELMTGQLPY 656 SNINNRDQII666 FMVGRGYLSP676 DLSKVRSNCP686 KAMKRLMAEC696 LKKKRDERPL 706 FPQILASIEL716 LARSLP
|
|||||
|
|
ILE463
3.407
GLY464
3.739
SER465
3.836
GLY466
3.158
SER467
2.771
PHE468
3.768
GLY469
3.674
VAL471
3.464
ALA481
3.573
LYS483
2.875
LEU514
3.560
THR529
3.529
|
|||||
| PDB ID: 7M0U Crystal structure of the BRAF:MEK1 kinases in complex with AMPPNP and Binimetinib | ||||||
| Method | X-ray diffraction | Resolution | 3.09 Å | Mutation | Yes | [1] |
| PDB Sequence |
DWEIPDGQIT
458 VGQRIGSGSF468 GTVYKGKWHG478 DVAVKMLNVT488 APTPQQLQAF498 KNEVGVLRKT 508 RHVNILLFMG518 YSTKPQLAIV528 TQWCEGSSLY538 HHLHIIETKF548 EMIKLIDIAR 558 QTAQGMDYLH568 AKSIIHRDLK578 SNNIFLHEDL588 TVKIGDFGLA598 TVKSRWSGSH 608 QFEQLSGSIL618 WMAPEVIRMQ628 DKNPYSFQSD638 VYAFGIVLYE648 LMTGQLPYSN 658 INNRDQIIFM668 VGRGYLSPDL678 SKVRSNCPKA688 MKRLMAECLK698 KKRDERPLFP 708 QILASIELLA718 RSLP
|
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|
|
ILE463
3.559
GLY464
3.685
SER465
3.735
GLY466
3.162
SER467
2.646
PHE468
3.567
GLY469
4.046
VAL471
3.392
ALA481
3.221
LYS483
3.020
LEU514
3.871
THR529
3.853
|
|||||
| PDB ID: 7M0W Crystal structure of the BRAF:MEK1 kinases in complex with AMPPNP and Pimasertib | ||||||
| Method | X-ray diffraction | Resolution | 3.09 Å | Mutation | Yes | [1] |
| PDB Sequence |
DDWEIPDGQI
457 TVGQRIGSGS467 FGTVYKGKWH477 GDVAVKMLNV487 TAPTPQQLQA497 FKNEVGVLRK 507 TRHVNILLFM517 GYSTKPQLAI527 VTQWCEGSSL537 YHHLHIIETK547 FEMIKLIDIA 557 RQTAQGMDYL567 HAKSIIHRDL577 KSNNIFLHED587 LTVKIGDFGL597 ATVKSRWSGS 607 HQFEQLSGSI617 LWMAPEVIRM627 QDKNPYSFQS637 DVYAFGIVLY647 ELMTGQLPYS 657 NINNRDQIIF667 MVGRGYLSPD677 LSKVRSNCPK687 AMKRLMAECL697 KKKRDERPLF 707 PQILASIELL717 ARSL
|
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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 .ANP or .ANP2 or .ANP3 or :3ANP;style chemicals stick;color identity;select .A:662 or .A:463 or .A:464 or .A:465 or .A:466 or .A:467 or .A:468 or .A:469 or .A:471 or .A:481 or .A:483 or .A:514 or .A:529 or .A:530 or .A:531 or .A:532 or .A:536 or .A:539 or .A:576 or .A:578 or .A:580 or .A:581 or .A:583 or .A:594; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
ARG662
4.924
ILE463
3.768
GLY464
3.756
SER465
3.572
GLY466
3.184
SER467
2.738
PHE468
3.704
GLY469
3.678
VAL471
3.684
ALA481
3.398
LYS483
2.787
LEU514
3.747
|
|||||
| PDB ID: 6V2W Crystal structure of the BRAF:MEK1 kinases in complex with AMPPNP | ||||||
| Method | X-ray diffraction | Resolution | 3.12 Å | Mutation | Yes | [1] |
| PDB Sequence |
SDDWEIPDGQ
456 ITVGQRIGSG466 SFGTVYKGKW476 HGDVAVKMLN486 VTAPTPQQLQ496 AFKNEVGVLR 506 KTRHVNILLF516 MGYSTKPQLA526 IVTQWCEGSS536 LYHHLHIIET546 KFEMIKLIDI 556 ARQTAQGMDY566 LHAKSIIHRD576 LKSNNIFLHE586 DLTVKIGDFG596 LATVKSRWSG 606 SHQFEQLSGS616 ILWMAPEVIR626 MQDKNPYSFQ636 SDVYAFGIVL646 YELMTGQLPY 656 SNINNRDQII666 FMVGRGYLSP676 DLSKVRSNCP686 KAMKRLMAEC696 LKKKRDERPL 706 FPQILASIEL716 LARSL
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ANP or .ANP2 or .ANP3 or :3ANP;style chemicals stick;color identity;select .A:463 or .A:464 or .A:465 or .A:466 or .A:467 or .A:468 or .A:469 or .A:470 or .A:471 or .A:481 or .A:483 or .A:514 or .A:529 or .A:530 or .A:531 or .A:532 or .A:536 or .A:539 or .A:576 or .A:578 or .A:580 or .A:581 or .A:583 or .A:594 or .A:662; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
ILE463
3.333
GLY464
3.599
SER465
3.703
GLY466
3.106
SER467
2.810
PHE468
3.777
GLY469
3.840
THR470
4.843
VAL471
3.542
ALA481
3.607
LYS483
3.062
LEU514
3.793
THR529
3.784
|
|||||
| PDB ID: 7M0Z Crystal structure of the BRAF:MEK1 kinases in complex with AMPPNP and CH5126766 | ||||||
| Method | X-ray diffraction | Resolution | 3.12 Å | Mutation | Yes | [1] |
| PDB Sequence |
DWEIPDGQIT
458 VGQRIGSGSF468 GTVYKGKWHG478 DVAVKMLNVT488 APTPQQLQAF498 KNEVGVLRKT 508 RHVNILLFMG518 YSTKPQLAIV528 TQWCEGSSLY538 HHLHIIETKF548 EMIKLIDIAR 558 QTAQGMDYLH568 AKSIIHRDLK578 SNNIFLHEDL588 TVKIGDFGLA598 TVKSRWSGSH 608 QFEQLSGSIL618 WMAPEVIRMQ628 DKNPYSFQSD638 VYAFGIVLYE648 LMTGQLPYSN 658 INNRDQIIFM668 VGRGYLSPDL678 SKVRSNCPKA688 MKRLMAECLK698 KKRDERPLFP 708 QILASIELLA718 RSL
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ANP or .ANP2 or .ANP3 or :3ANP;style chemicals stick;color identity;select .A:463 or .A:464 or .A:465 or .A:466 or .A:467 or .A:468 or .A:469 or .A:471 or .A:481 or .A:483 or .A:514 or .A:529 or .A:530 or .A:531 or .A:532 or .A:536 or .A:539 or .A:576 or .A:578 or .A:580 or .A:581 or .A:583 or .A:594; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
ILE463
3.409
GLY464
3.881
SER465
3.705
GLY466
3.111
SER467
2.802
PHE468
3.744
GLY469
3.796
VAL471
3.557
ALA481
3.456
LYS483
3.254
LEU514
3.612
THR529
4.137
|
|||||
| PDB ID: 7M0V Crystal structure of the BRAF:MEK1 kinases in complex with AMPPNP and Cobimetinib | ||||||
| Method | X-ray diffraction | Resolution | 3.16 Å | Mutation | Yes | [1] |
| PDB Sequence |
DWEIPDGQIT
458 VGQRIGSGSF468 GTVYKGKWHG478 DVAVKMLNVT488 APTPQQLQAF498 KNEVGVLRKT 508 RHVNILLFMG518 YSTKPQLAIV528 TQWCEGSSLY538 HHLHIIETKF548 EMIKLIDIAR 558 QTAQGMDYLH568 AKSIIHRDLK578 SNNIFLHEDL588 TVKIGDFGLA598 TVKSRWSGSH 608 QFEQLSGSIL618 WMAPEVIRMQ628 DKNPYSFQSD638 VYAFGIVLYE648 LMTGQLPYSN 658 INNRDQIIFM668 VGRGYLSPDL678 SKVRSNCPKA688 MKRLMAECLK698 KKRDERPLFP 708 QILASIELLA718 RSLP
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ANP or .ANP2 or .ANP3 or :3ANP;style chemicals stick;color identity;select .A:463 or .A:464 or .A:465 or .A:466 or .A:467 or .A:468 or .A:469 or .A:471 or .A:481 or .A:483 or .A:514 or .A:529 or .A:530 or .A:531 or .A:532 or .A:536 or .A:539 or .A:576 or .A:578 or .A:580 or .A:581 or .A:583 or .A:594; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
ILE463
3.722
GLY464
3.849
SER465
4.223
GLY466
3.022
SER467
2.621
PHE468
3.258
GLY469
3.666
VAL471
3.717
ALA481
3.297
LYS483
3.217
LEU514
3.533
THR529
3.773
|
|||||
| PDB ID: 7M0T Crystal structure of the BRAF:MEK1 kinases in complex with AMPPNP and Selumetinib | ||||||
| Method | X-ray diffraction | Resolution | 3.19 Å | Mutation | Yes | [1] |
| PDB Sequence |
DDWEIPDGQI
457 TVGQRIGSGS467 FGTVYKGKWH477 GDVAVKMLNV487 TAPTPQQLQA497 FKNEVGVLRK 507 TRHVNILLFM517 GYSTKPQLAI527 VTQWCEGSSL537 YHHLHIIETK547 FEMIKLIDIA 557 RQTAQGMDYL567 HAKSIIHRDL577 KSNNIFLHED587 LTVKIGDFGL597 ATVKSRWSGS 607 HQFEQLSGSI617 LWMAPEVIRM627 QDKNPYSFQS637 DVYAFGIVLY647 ELMTGQLPYS 657 NINNRDQIIF667 MVGRGYLSPD677 LSKVRSNCPK687 AMKRLMAECL697 KKKRDERPLF 707 PQILASIELL717 ARSL
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ANP or .ANP2 or .ANP3 or :3ANP;style chemicals stick;color identity;select .A:463 or .A:464 or .A:465 or .A:466 or .A:467 or .A:468 or .A:469 or .A:471 or .A:481 or .A:483 or .A:514 or .A:529 or .A:530 or .A:531 or .A:532 or .A:536 or .A:539 or .A:576 or .A:578 or .A:580 or .A:581 or .A:583 or .A:594; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
ILE463
3.657
GLY464
3.818
SER465
3.811
GLY466
3.045
SER467
2.732
PHE468
3.481
GLY469
3.769
VAL471
3.605
ALA481
3.417
LYS483
2.904
LEU514
3.548
THR529
3.926
|
|||||
| PDB ID: 7M0Y Crystal structure of the BRAF:MEK1 kinases in complex with AMPPNP and Trametinib | ||||||
| Method | X-ray diffraction | Resolution | 3.45 Å | Mutation | Yes | [1] |
| PDB Sequence |
SDDWEIPDGQ
456 ITVGQRIGSG466 SFGTVYKGKW476 HGDVAVKMLN486 VTAPTPQQLQ496 AFKNEVGVLR 506 KTRHVNILLF516 MGYSTKPQLA526 IVTQWCEGSS536 LYHHLHIIET546 KFEMIKLIDI 556 ARQTAQGMDY566 LHAKSIIHRD576 LKSNNIFLHE586 DLTVKIGDFG596 LATVKSRWSG 606 SHQFEQLSGS616 ILWMAPEVIR626 MQDKNPYSFQ636 SDVYAFGIVL646 YELMTGQLPY 656 SNINNRDQII666 FMVGRGYLSP676 DLSKVRSNCP686 KAMKRLMAEC696 LKKKRDERPL 706 FPQILASIEL716 LARSL
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ANP or .ANP2 or .ANP3 or :3ANP;style chemicals stick;color identity;select .A:463 or .A:464 or .A:465 or .A:466 or .A:467 or .A:468 or .A:469 or .A:470 or .A:471 or .A:481 or .A:483 or .A:514 or .A:529 or .A:530 or .A:531 or .A:532 or .A:536 or .A:539 or .A:576 or .A:578 or .A:580 or .A:581 or .A:583 or .A:594; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
ILE463
3.257
GLY464
3.418
SER465
3.793
GLY466
3.016
SER467
2.844
PHE468
3.809
GLY469
3.545
THR470
4.912
VAL471
3.437
ALA481
3.171
LYS483
3.213
LEU514
3.796
|
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Allosteric MEK inhibitors act on BRAF/MEK complexes to block MEK activation. Proc Natl Acad Sci U S A. 2021 Sep 7;118(36):e2107207118. | ||||
| REF 2 | Architecture of autoinhibited and active BRAF-MEK1-14-3-3 complexes. Nature. 2019 Nov;575(7783):545-550. | ||||
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