Binding Site Information of Target

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Target General Information
Drug Binding Sites of Target
References
Target General Information  Top
Target ID T07087 Target Info
Target Name Focal adhesion kinase 2 (PTK2B)
Synonyms Related adhesion focal tyrosine kinase; RAFTK; Protein-tyrosine kinase 2-beta; Proline-rich tyrosine kinase 2; PYK2; FAK2; FADK 2; Cell adhesion kinase beta; Calcium-regulated non-receptor proline-rich tyrosine kinase; Calcium-dependent tyrosine kinase; CAKB; CAK-beta; CADTK
Target Type Literature-reported Target
Gene Name PTK2B
Biochemical Class Kinase
UniProt ID
FAK2_HUMAN
Drug Binding Sites of Target  Top
Ligand Name: PF-562271 Ligand Info
Structure Description Selectivity switch between FAK and Pyk2: Macrocyclization of FAK inhibitors improves Pyk2 potency PDB:5TOB
Method X-ray diffraction Resolution 2.12 Å Mutation No [1]
PDB Sequence
IAREDVVLNR
429
ILGEGFFGEV
439
YEGVYTHKGE
450
KINVAVKTCK
460
DNKEKFMSEA
475

VIMKNLDHPH
485
IVKLIGIIEP
497
TWIIMELYPY
507
GELGHYLERN
517
KNSLKVLTLV
527

LYSLQICKAM
537
AYLESINCVH
547
RDIAVRNILV
557
ASPECVKLGD
567
FGPIKWMSPE
595

SINFRRFTTA
605
SDVWMFAVCM
615
WEILSFGKQP
625
FFWLENKDVI
635
GVLEKGDRLP
645

KPDLCPPVLY
655
TLMTRCWDYD
665
PSDRPRFTEL
675
VCSLSDVYQM
685
EKDIA
Residue
Distance (Å)
LEU431
3.590
GLY432
2.989
GLU433
3.214
GLY434
4.163
VAL439
3.650
ALA455
4.036
LYS457
4.357
VAL487
3.438
LYS488
4.988
MET502
3.379
GLU503
3.177
Residue
Distance (Å)
LEU504
3.321
TYR505
2.999
PRO506
4.078
GLY508
3.878
GLU509
3.124
ARG553
3.216
ASN554
3.979
LEU556
3.597
GLY566
4.919
ASP567
3.926
Ligand Name: Doramapimod Ligand Info
Structure Description Crystal Structure of PYK2 complexed with BIRB796 PDB:3FZS
Method X-ray diffraction Resolution 1.75 Å Mutation No [2]
PDB Sequence
IAREDVVLNR
429
ILGEGFFGEV
439
YEGVYTNHKG
449
EKINVAVKTC
459
KKDCTLDNKE
469

KFMSEAVIMK
479
NLDHPHIVKL
489
IGIIEEEPTW
499
IIMELYPYGE
509
LGHYLERNKN
519

SLKVLTLVLY
529
SLQICKAMAY
539
LESINCVHRD
549
IAVRNILVAS
559
PECVKLGDFG
569

LPIKWMSPES
596
INFRRFTTAS
606
DVWMFAVCMW
616
EILSFGKQPF
626
FWLENKDVIG
636

VLEKGDRLPK
646
PDLCPPVLYT
656
LMTRCWDYDP
666
SDRPRFTELV
676
CSLSDVYQME
686

KDIA
Residue
Distance (Å)
LEU431
3.832
VAL439
4.074
ALA455
3.837
LYS457
4.088
LYS470
4.332
SER473
3.639
GLU474
2.756
ILE477
3.919
MET478
3.640
LEU481
3.229
ILE486
4.045
VAL487
3.462
Residue
Distance (Å)
LYS488
4.770
MET502
3.412
GLU503
3.423
LEU504
3.743
GLU509
3.485
LEU540
4.025
HIS547
3.829
LEU556
3.674
LEU565
3.645
GLY566
3.622
ASP567
2.963
PHE568
3.443
Ligand Name: 7-({[3-Tert-Butyl-1-(4-Methylphenyl)-1h-Pyrazol-5-Yl]carbamoyl}amino)-N-(Propan-2-Yl)-1h-Indole-2-Carboxamide Ligand Info
Structure Description Crystal structure of PYK2 with the indole 10c PDB:4H1M
Method X-ray diffraction Resolution 1.99 Å Mutation No [3]
PDB Sequence
IAREDVVLNR
429
ILGEGFFGEV
439
YEGVYTNHKG
449
EKINVAVKTC
459
KKDCTLDNKE
469

KFMSEAVIMK
479
NLDHPHIVKL
489
IGIIEEEPTW
499
IIMELYPYGE
509
LGHYLERNKN
519

SLKVLTLVLY
529
SLQICKAMAY
539
LESINCVHRD
549
IAVRNILVAS
559
PECVKLGDFG
569

LSLPIKWMSP
594
ESINFRRFTT
604
ASDVWMFAVC
614
MWEILSFGKQ
624
PFFWLENKDV
634

IGVLEKGDRL
644
PKPDLCPPVL
654
YTLMTRCWDY
664
DPSDRPRFTE
674
LVCSLSDVYQ
684

MEKDIA
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .0YJ or .0YJ2 or .0YJ3 or :30YJ;style chemicals stick;color identity;select .A:431 or .A:432 or .A:433 or .A:434 or .A:439 or .A:455 or .A:457 or .A:470 or .A:473 or .A:474 or .A:477 or .A:478 or .A:481 or .A:486 or .A:487 or .A:502 or .A:503 or .A:504 or .A:540 or .A:547 or .A:556 or .A:565 or .A:566 or .A:567 or .A:568 or .A:570; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
LEU431
4.268
GLY432
3.677
GLU433
3.742
GLY434
4.154
VAL439
3.728
ALA455
3.690
LYS457
2.911
LYS470
4.077
SER473
3.937
GLU474
2.708
ILE477
4.447
MET478
3.515
LEU481
3.537
Residue
Distance (Å)
ILE486
3.838
VAL487
3.117
MET502
3.605
GLU503
4.160
LEU504
4.429
LEU540
4.075
HIS547
3.388
LEU556
4.426
LEU565
3.522
GLY566
3.406
ASP567
2.982
PHE568
3.208
LEU570
4.990
Ligand Name: 1-[3-Tert-Butyl-1-(4-Methylphenyl)-1h-Pyrazol-5-Yl]-3-[3-(4-Methoxy-2-Methylphenyl)-1h-Pyrazol-5-Yl]urea Ligand Info
Structure Description Crystal structure of PYK2 with the pyrazole 13a PDB:4H1J
Method X-ray diffraction Resolution 2.00 Å Mutation No [3]
PDB Sequence
GIAREDVVLN
428
RILGEGFFGE
438
VYEGVYTNHK
448
GEKINVAVKT
458
CKKDCTLDNK
468

EKFMSEAVIM
478
KNLDHPHIVK
488
LIGIIEEEPT
498
WIIMELYPYG
508
ELGHYLERNK
518

NSLKVLTLVL
528
YSLQICKAMA
538
YLESINCVHR
548
DIAVRNILVA
558
SPECVKLGDF
568

GLSRDEVTRL
587
PIKWMSPESI
597
NFRRFTTASD
607
VWMFAVCMWE
617
ILSFGKQPFF
627

WLENKDVIGV
637
LEKGDRLPKP
647
DLCPPVLYTL
657
MTRCWDYDPS
667
DRPRFTELVC
677

SLSDVYQMEK
687
DIA
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .0YH or .0YH2 or .0YH3 or :30YH;style chemicals stick;color identity;select .A:431 or .A:455 or .A:457 or .A:470 or .A:473 or .A:474 or .A:477 or .A:478 or .A:481 or .A:486 or .A:487 or .A:502 or .A:503 or .A:504 or .A:505 or .A:508 or .A:540 or .A:547 or .A:556 or .A:565 or .A:566 or .A:567 or .A:568 or .A:572 or .A:576; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
LEU431
4.028
ALA455
4.386
LYS457
3.065
LYS470
4.154
SER473
3.493
GLU474
2.736
ILE477
3.993
MET478
3.537
LEU481
3.984
ILE486
3.786
VAL487
3.297
MET502
3.868
GLU503
3.225
Residue
Distance (Å)
LEU504
3.711
TYR505
3.118
GLY508
4.515
LEU540
3.806
HIS547
3.909
LEU556
3.486
LEU565
3.595
GLY566
3.404
ASP567
2.892
PHE568
3.559
ARG572
3.435
ASP576
3.985
Ligand Name: 25-(Methylsulfonyl)-8-(Trifluoromethyl)-5,17,18,21,22,23,24,25-Octahydro-12h-7,11-(Azeno)-16,13-(Metheno)pyrido[3,2-I]pyrrolo[1,2-Q][1,3,7,11,17]pentaazacyclohenicosin-20(6h)-One Ligand Info
Structure Description Selectivity switch between FAK and Pyk2: Macrocyclization of FAK inhibitors improves Pyk2 potency PDB:5TO8
Method X-ray diffraction Resolution 1.98 Å Mutation No [1]
PDB Sequence
IAREDVVLNR
429
ILGEGFFGEV
439
YEGVYTNHKG
449
EKINVAVKTC
459
KKDCTNKEKF
471

MSEAVIMKNL
481
DHPHIVKLIG
491
IIEPTWIIME
503
LYPYGELGHY
513
LERNKNSLKV
523

LTLVLYSLQI
533
CKAMAYLESC
545
VHRDIAVRNI
555
LVASPECVKL
565
GDFGLSRIKW
591

MSPESINFRR
601
FTTASDVWMF
611
AVCMWEILSF
621
GKQPFFWLEN
631
KDVIGVLEKG
641

DRLPKPDLCP
651
PVLYTLMTRC
661
WDYDPSDRPR
671
FTELVCSLSD
681
VYQMEKDIAM
691
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .7FM or .7FM2 or .7FM3 or :37FM;style chemicals stick;color identity;select .A:431 or .A:432 or .A:433 or .A:434 or .A:439 or .A:441 or .A:455 or .A:457 or .A:487 or .A:488 or .A:502 or .A:503 or .A:504 or .A:505 or .A:506 or .A:508 or .A:509 or .A:553 or .A:554 or .A:556 or .A:566 or .A:567; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
LEU431
3.514
GLY432
2.988
GLU433
3.383
GLY434
3.874
VAL439
3.777
GLU441
3.886
ALA455
3.819
LYS457
4.663
VAL487
3.540
LYS488
4.946
MET502
3.326
Residue
Distance (Å)
GLU503
3.170
LEU504
3.530
TYR505
2.629
PRO506
4.056
GLY508
3.675
GLU509
3.259
ARG553
3.359
ASN554
3.878
LEU556
3.621
GLY566
4.870
ASP567
3.089
Ligand Name: 1-(3-(tert-butyl)-1-(p-tolyl)-1H-pyrazol-5-yl)-3-(3-((pyridin-3-yloxy)methyl)-1H-pyrazol-5-yl)urea Ligand Info
Structure Description Crystal structure of PYK2 complexed with PF-4618433 PDB:3FZT
Method X-ray diffraction Resolution 1.95 Å Mutation No [2]
PDB Sequence
IAREDVVLNR
429
ILGEGFFGEV
439
YEGVYTNHKG
449
EKINVAVKTC
459
KKDCTLDNKE
469

KFMSEAVIMK
479
NLDHPHIVKL
489
IGIIEEEPTW
499
IIMELYPYGE
509
LGHYLERNKN
519

SLKVLTLVLY
529
SLQICKAMAY
539
LESINCVHRD
549
IAVRNILVAS
559
PECVKLGDFG
569

LSRDELPIKW
591
MSPESINFRR
601
FTTASDVWMF
611
AVCMWEILSF
621
GKQPFFWLEN
631

KDVIGVLEKG
641
DRLPKPDLCP
651
PVLYTLMTRC
661
WDYDPSDRPR
671
FTELVCSLSD
681

VYQMEKDIA
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .4JZ or .4JZ2 or .4JZ3 or :34JZ;style chemicals stick;color identity;select .A:431 or .A:455 or .A:457 or .A:470 or .A:473 or .A:474 or .A:477 or .A:478 or .A:481 or .A:486 or .A:487 or .A:502 or .A:503 or .A:504 or .A:505 or .A:508 or .A:540 or .A:547 or .A:556 or .A:565 or .A:566 or .A:567 or .A:568 or .A:572 or .A:576; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
LEU431
4.116
ALA455
4.407
LYS457
2.919
LYS470
4.383
SER473
3.476
GLU474
2.706
ILE477
3.814
MET478
3.523
LEU481
3.792
ILE486
3.764
VAL487
3.340
MET502
3.647
GLU503
3.319
Residue
Distance (Å)
LEU504
3.455
TYR505
2.782
GLY508
4.418
LEU540
3.763
HIS547
3.987
LEU556
3.314
LEU565
3.607
GLY566
3.357
ASP567
2.865
PHE568
3.458
ARG572
3.318
ASP576
3.866
Ligand Name: 4-{[4-{[(1R,2R)-2-(dimethylamino)cyclopentyl]amino}-5-(trifluoromethyl)pyrimidin-2-yl]amino}-N-methylbenzenesulfonamide Ligand Info
Structure Description Crystal structure of PYK2 in complex with Sulfoximine-substituted trifluoromethylpyrimidine analog PDB:3H3C
Method X-ray diffraction Resolution 2.00 Å Mutation No [4]
PDB Sequence
PQYGIAREDV
425
VLNRILGEGF
435
FGEVYEGVYT
445
NHKGEKINVA
455
VKTCKKDCTL
465

DNKEKFMSEA
475
VIMKNLDHPH
485
IVKLIGIIEE
495
EPTWIIMELY
505
PYGELGHYLE
515

RNKNSLKVLT
525
LVLYSLQICK
535
AMAYLESINC
545
VHRDIAVRNI
555
LVASPECVKL
565

GDFGLTRLPI
589
KWMSPESINF
599
RRFTTASDVW
609
MFAVCMWEIL
619
SFGKQPFFWL
629

ENKDVIGVLE
639
KGDRLPKPDL
649
CPPVLYTLMT
659
RCWDYDPSDR
669
PRFTELVCSL
679

SDVYQMEKDI
689
AME
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .P1E or .P1E2 or .P1E3 or :3P1E;style chemicals stick;color identity;select .A:431 or .A:432 or .A:433 or .A:434 or .A:439 or .A:455 or .A:457 or .A:487 or .A:502 or .A:503 or .A:504 or .A:505 or .A:506 or .A:507 or .A:508 or .A:509 or .A:512 or .A:553 or .A:554 or .A:556 or .A:567; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
LEU431
3.698
GLY432
4.243
GLU433
4.125
GLY434
4.451
VAL439
3.779
ALA455
3.957
LYS457
4.046
VAL487
3.860
MET502
3.398
GLU503
3.246
LEU504
3.524
Residue
Distance (Å)
TYR505
2.998
PRO506
4.200
TYR507
4.922
GLY508
3.623
GLU509
3.042
HIS512
3.417
ARG553
3.850
ASN554
4.047
LEU556
3.514
ASP567
3.310
Ligand Name: Phosphothiophosphoric acid-adenylate ester Ligand Info
Structure Description Crystal structure of PYK2 complexed with ATPgS PDB:3FZP
Method X-ray diffraction Resolution 2.10 Å Mutation No [2]
PDB Sequence
GIAREDVVLN
428
RILGEGFFGE
438
VYEGVYTNHK
448
GEKINVAVKT
458
CKKDCTLDNK
468

EKFMSEAVIM
478
KNLDHPHIVK
488
LIGIIEEEPT
498
WIIMELYPYG
508
ELGHYLERNK
518

NSLKVLTLVL
528
YSLQICKAMA
538
YLESINCVHR
548
DIAVRNILVA
558
SPECVKLGDF
568

GTRLPIKWMS
593
PESINFRRFT
603
TASDVWMFAV
613
CMWEILSFGK
623
QPFFWLENKD
633

VIGVLEKGDR
643
LPKPDLCPPV
653
LYTLMTRCWD
663
YDPSDRPRFT
673
ELVCSLSDVY
683

QMEKDIAME
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .AGS or .AGS2 or .AGS3 or :3AGS;style chemicals stick;color identity;select .A:431 or .A:432 or .A:433 or .A:434 or .A:435 or .A:436 or .A:437 or .A:439 or .A:455 or .A:457 or .A:458 or .A:471 or .A:474 or .A:502 or .A:503 or .A:504 or .A:505 or .A:509 or .A:554 or .A:556 or .A:567 or .A:568; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
LEU431
3.811
GLY432
4.228
GLU433
3.865
GLY434
3.077
PHE435
2.365
PHE436
3.198
GLY437
4.062
VAL439
3.582
ALA455
3.633
LYS457
2.568
THR458
4.841
Residue
Distance (Å)
PHE471
4.406
GLU474
3.257
MET502
3.961
GLU503
2.631
LEU504
3.675
TYR505
2.972
GLU509
2.955
ASN554
4.706
LEU556
3.564
ASP567
3.844
PHE568
2.406
Ligand Name: 5-{[4-{[2-(pyrrolidin-1-ylsulfonyl)benzyl]amino}-5-(trifluoromethyl)pyrimidin-2-yl]amino}-1,3-dihydro-2H-indol-2-one Ligand Info
Structure Description Crystal structure of PYK2 complexed with PF-2318841 PDB:3ET7
Method X-ray diffraction Resolution 2.70 Å Mutation No [5]
PDB Sequence
GIAREDVVLN
428
RILGEGFFGE
438
VYEGVYTNHK
448
GEKINVAVKT
458
CKKDCTLDNK
468

EKFMSEAVIM
478
KNLDHPHIVK
488
LIGIIEEEPT
498
WIIMELYPYG
508
ELGHYLERNK
518

NSLKVLTLVL
528
YSLQICKAMA
538
YLESINCVHR
548
DIAVRNILVA
558
SPECVKLGDF
568

GLSRTRLPIK
590
WMSPESINFR
600
RFTTASDVWM
610
FAVCMWEILS
620
FGKQPFFWLE
630

NKDVIGVLEK
640
GDRLPKPDLC
650
PPVLYTLMTR
660
CWDYDPSDRP
670
RFTELVCSLS
680

DVYQMEKDIA
690
M
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .349 or .3492 or .3493 or :3349;style chemicals stick;color identity;select .A:431 or .A:432 or .A:433 or .A:434 or .A:439 or .A:455 or .A:487 or .A:502 or .A:503 or .A:504 or .A:505 or .A:506 or .A:507 or .A:508 or .A:509 or .A:553 or .A:554 or .A:556 or .A:566 or .A:567; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
LEU431
3.461
GLY432
3.911
GLU433
3.746
GLY434
4.519
VAL439
3.740
ALA455
3.809
VAL487
3.685
MET502
3.416
GLU503
3.073
LEU504
3.128
Residue
Distance (Å)
TYR505
2.821
PRO506
4.353
TYR507
4.847
GLY508
3.842
GLU509
3.488
ARG553
3.083
ASN554
4.306
LEU556
3.503
GLY566
4.347
ASP567
4.000
Ligand Name: N-Methyl-N-[2-[[[2-[(2-oxo-2,3-dihydro-1H-indol-5-YL)amino]-5-trifluoromethylpyrimidin-4-YL]amino]methyl]phenyl]methanesulfonamide Ligand Info
Structure Description Crystal structure of PYK2 complexed with PF-431396 PDB:3FZR
Method X-ray diffraction Resolution 2.70 Å Mutation No [2]
PDB Sequence
GIAREDVVLN
428
RILGEGFFGE
438
VYEGVYTNHK
448
GEKINVAVKT
458
CKKDCTLDNK
468

EKFMSEAVIM
478
KNLDHPHIVK
488
LIGIIEEEPT
498
WIIMELYPYG
508
ELGHYLERNK
518

NSLKVLTLVL
528
YSLQICKAMA
538
YLESINCVHR
548
DIAVRNILVA
558
SPECVKLGDF
568

GLSRTRLPIK
590
WMSPESINFR
600
RFTTASDVWM
610
FAVCMWEILS
620
FGKQPFFWLE
630

NKDVIGVLEK
640
GDRLPKPDLC
650
PPVLYTLMTR
660
CWDYDPSDRP
670
RFTELVCSLS
680

DVYQMEKDIA
690
M
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .3JZ or .3JZ2 or .3JZ3 or :33JZ;style chemicals stick;color identity;select .A:431 or .A:432 or .A:433 or .A:434 or .A:439 or .A:455 or .A:487 or .A:502 or .A:503 or .A:504 or .A:505 or .A:506 or .A:508 or .A:509 or .A:553 or .A:554 or .A:556 or .A:566 or .A:567; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
LEU431
3.411
GLY432
2.964
GLU433
3.601
GLY434
3.694
VAL439
3.273
ALA455
3.819
VAL487
3.619
MET502
3.115
GLU503
2.904
LEU504
3.440
Residue
Distance (Å)
TYR505
2.892
PRO506
3.962
GLY508
3.675
GLU509
3.383
ARG553
3.229
ASN554
4.618
LEU556
3.419
GLY566
4.142
ASP567
3.805
References  Top
REF 1 Selectivity switch between FAK and Pyk2: Macrocyclization of FAK inhibitors improves Pyk2 potency. Bioorg Med Chem Lett. 2016 Dec 15;26(24):5926-5930.
REF 2 Structural characterization of proline-rich tyrosine kinase 2 (PYK2) reveals a unique (DFG-out) conformation and enables inhibitor design. J Biol Chem. 2009 May 8;284(19):13193-201
REF 3 Identification of novel series of pyrazole and indole-urea based DFG-out PYK2 inhibitors. Bioorg Med Chem Lett. 2012 Dec 15;22(24):7523-9.
REF 4 Sulfoximine-substituted trifluoromethylpyrimidine analogs as inhibitors of proline-rich tyrosine kinase 2 (PYK2) show reduced hERG activity. Bioorg Med Chem Lett. 2009 Jun 15;19(12):3253-8.
REF 5 Trifluoromethylpyrimidine-based inhibitors of proline-rich tyrosine kinase 2 (PYK2): structure-activity relationships and strategies for the elimination of reactive metabolite formation. Bioorg Med Chem Lett. 2008 Dec 1;18(23):6071-7.

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