Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T62431 | Target Info | |||
| Target Name | Tyrosine-protein kinase SYK (SYK) | ||||
| Synonyms | p72-Syk; Spleen tyrosine kinase | ||||
| Target Type | Successful Target | ||||
| Gene Name | SYK | ||||
| Biochemical Class | Kinase | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | Phosphonotyrosine | Ligand Info | |||
| Canonical SMILES | C1=CC(=CC=C1CC(C(=O)O)N)OP(=O)(O)O | ||||
| InChI | 1S/C9H12NO6P/c10-8(9(11)12)5-6-1-3-7(4-2-6)16-17(13,14)15/h1-4,8H,5,10H2,(H,11,12)(H2,13,14,15)/t8-/m0/s1 | ||||
| InChIKey | DCWXELXMIBXGTH-QMMMGPOBSA-N | ||||
| PubChem Compound ID | 30819 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 5C26 Crystal structure of SYK in complex with compound 1 | ||||||
| Method | X-ray diffraction | Resolution | 1.95 Å | Mutation | No | [1] |
| PDB Sequence |
VYLDRKLLTL
372 EDKELGSGNF382 GTVKKGYYQM392 KKVVKTVAVK402 ILKNEANDPA412 LKDELLAEAN 422 VMQQLDNPYI432 VRMIGICEAE442 SWMLVMEMAE452 LGPLNKYLQQ462 NRHVKDKNII 472 ELVHQVSMGM482 KYLEESNFVH492 RDLAARNVLL502 VTQHYAKISD512 FGLSKALRAD 522 ENKAQTHGKW534 PVKWYAPECI544 NYYKFSSKSD554 VWSFGVLMWE564 AFSYGQKPYR 574 GMKGSEVTAM584 LEKGERMGCP594 AGCPREMYDL604 MNLCWTYDVE614 NRPGFAAVEL 624 RLRNYYYDVV634 NH
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VAL491
4.380
ARG493
3.778
LYS517
2.754
LEU519
3.494
GLU523
3.196
ASN524
1.329
LYS527
1.342
ALA528
3.700
GLN529
3.535
TYR547
3.478
LYS548
3.003
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| PDB ID: 5C27 Crystal structure of SYK in complex with compound 2 | ||||||
| Method | X-ray diffraction | Resolution | 2.15 Å | Mutation | No | [1] |
| PDB Sequence |
VYLDRKLLTL
372 EDKELGSGNF382 GTVKKGYYQM392 KKVVKTVAVK402 ILKNEANDPA412 LKDELLAEAN 422 VMQQLDNPYI432 VRMIGICEAE442 SWMLVMEMAE452 LGPLNKYLQQ462 NRHVKDKNII 472 ELVHQVSMGM482 KYLEESNFVH492 RDLAARNVLL502 VTQHYAKISD512 FGLSKALRAD 522 ENKAQTHGKW534 PVKWYAPECI544 NYYKFSSKSD554 VWSFGVLMWE564 AFSYGQKPYR 574 GMKGSEVTAM584 LEKGERMGCP594 AGCPREMYDL604 MNLCWTYDVE614 NRPGFAAVEL 624 RLRNYYYDVV634 NH
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| PDB ID: 4YJR SYK kinase domain in complex with inhibitor GTC000225 | ||||||
| Method | X-ray diffraction | Resolution | 1.32 Å | Mutation | No | [2] |
| PDB Sequence |
YLDRKLLTLE
373 DKELGTVKKG388 YYQMKKVVKT398 VAVKILKNEA408 NDPALKDELL418 AEANVMQQLD 428 NPYIVRMIGI438 CEAESWMLVM448 EMAELGPLNK458 YLQQNRHVKD468 KNIIELVHQV 478 SMGMKYLEES488 NFVHRDLAAR498 NVLLVTQHYA508 KISDFGLSKA518 LRADENKAQT 530 HGKWPVKWYA540 PECINYYKFS550 SKSDVWSFGV560 LMWEAFSYGQ570 KPYRGMKGSE 580 VTAMLEKGER590 MGCPAGCPRE600 MYDLMNLCWT610 YDVENRPGFA620 AVELRLRNYY 630 YDV
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| PDB ID: 4YJQ SYK kinase domain in complex with inhibitor GTC000224 | ||||||
| Method | X-ray diffraction | Resolution | 1.34 Å | Mutation | No | [2] |
| PDB Sequence |
YLDRKLLTLE
373 DKELGGTVKK387 GYYQMKKVVK397 TVAVKILKNE407 ANDPALKDEL417 LAEANVMQQL 427 DNPYIVRMIG437 ICEAESWMLV447 MEMAELGPLN457 KYLQQNRHVK467 DKNIIELVHQ 477 VSMGMKYLEE487 SNFVHRDLAA497 RNVLLVTQHY507 AKISDFGLSK517 ALRADENKAQ 529 THGKWPVKWY539 APECINYYKF549 SSKSDVWSFG559 VLMWEAFSYG569 QKPYRGMKGS 579 EVTAMLEKGE589 RMGCPAGCPR599 EMYDLMNLCW609 TYDVENRPGF619 AAVELRLRNY 629 YYDV
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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:491 or .A:493 or .A:517 or .A:519 or .A:520 or .A:523 or .A:524 or .A:527 or .A:528 or .A:529 or .A:547 or .A:548 or .A:549 or .A:550; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 4YJT THE KINASE DOMAIN OF HUMAN SPLEEN TYROSINE (SYK) IN COMPLEX WITH GTC000233 | ||||||
| Method | X-ray diffraction | Resolution | 1.52 Å | Mutation | No | [2] |
| PDB Sequence |
YLDRKLLTLE
373 DKELGSGNFG383 TVKKGYYQMK393 KVVKTVAVKI403 LKNEANDPAL413 KDELLAEANV 423 MQQLDNPYIV433 RMIGICEAES443 WMLVMEMAEL453 GPLNKYLQQN463 RHVKDKNIIE 473 LVHQVSMGMK483 YLEESNFVHR493 DLAARNVLLV503 TQHYAKISDF513 GLSKALRADE 523 NKAQTHGKWP535 VKWYAPECIN545 YYKFSSKSDV555 WSFGVLMWEA565 FSYGQKPYRG 575 MKGSEVTAML585 EKGERMGCPA595 GCPREMYDLM605 NLCWTYDVEN615 RPGFAAVELR 625 LRNYYYDV
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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:491 or .A:493 or .A:517 or .A:519 or .A:523 or .A:524 or .A:527 or .A:528 or .A:529 or .A:547 or .A:548 or .A:549 or .A:550; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 4YJV THE KINASE DOMAIN OF HUMAN SPLEEN TYROSINE (SYK) IN COMPLEX WITH GTC000250 | ||||||
| Method | X-ray diffraction | Resolution | 1.65 Å | Mutation | No | [3] |
| PDB Sequence |
YLDRKLLTLE
373 DKELGTVKKG388 YYQMKKVVKT398 VAVKILKNEA408 NDPALKDELL418 AEANVMQQLD 428 NPYIVRMIGI438 CEAESWMLVM448 EMAELGPLNK458 YLQQNRHVKD468 KNIIELVHQV 478 SMGMKYLEES488 NFVHRDLAAR498 NVLLVTQHYA508 KISDFGLSKA518 LRADENKAQT 530 HGKWPVKWYA540 PECINYYKFS550 SKSDVWSFGV560 LMWEAFSYGQ570 KPYRGMKGSE 580 VTAMLEKGER590 MGCPAGCPRE600 MYDLMNLCWT610 YDVENRPGFA620 AVELRLRNYY 630 YDV
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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:491 or .A:493 or .A:517 or .A:519 or .A:523 or .A:524 or .A:527 or .A:528 or .A:547 or .A:548 or .A:549 or .A:550; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 4YJU THE KINASE DOMAIN OF HUMAN SPLEEN TYROSINE (SYK) IN COMPLEX WITH GTC000249 | ||||||
| Method | X-ray diffraction | Resolution | 1.67 Å | Mutation | No | [2] |
| PDB Sequence |
YLDRKLLTLE
373 DKELGSGNFG383 TVKKGYYQMK393 KVVKTVAVKI403 LKNEANDPAL413 KDELLAEANV 423 MQQLDNPYIV433 RMIGICEAES443 WMLVMEMAEL453 GPLNKYLQQN463 RHVKDKNIIE 473 LVHQVSMGMK483 YLEESNFVHR493 DLAARNVLLV503 TQHYAKISDF513 GLSKALRADE 523 NKAGKWPVKW538 YAPECINYYK548 FSSKSDVWSF558 GVLMWEAFSY568 GQKPYRGMKG 578 SEVTAMLEKG588 ERMGCPAGCP598 REMYDLMNLC608 WTYDVENRPG618 FAAVELRLRN 628 YYYDV
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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:491 or .A:493 or .A:517 or .A:519 or .A:523 or .A:524 or .A:527 or .A:528 or .A:547 or .A:548 or .A:549 or .A:550; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 5LMA HUMAN SPLEEN TYROSINE KINASE KINASE DOMAIN IN COMPLEX WITH AZANAPHTHYRIDINE INHIBITOR | ||||||
| Method | X-ray diffraction | Resolution | 1.43 Å | Mutation | No | [4] |
| PDB Sequence |
VYLDRKLLTL
372 EDKELGSGNF382 GTVKKGYYQM392 KKVVKTVAVK402 ILKNEANDPA412 LKDELLAEAN 422 VMQQLDNPYI432 VRMIGICEAE442 SWMLVMEMAE452 LGPLNKYLQQ462 NRHVKDKNII 472 ELVHQVSMGM482 KYLEESNFVH492 RDLAARNVLL502 VTQHYAKISD512 FGLSKALRAD 522 ENYKAQGKWP535 VKWYAPECIN545 YYKFSSKSDV555 WSFGVLMWEA565 FSYGQKPYRG 575 MKGSEVTAML585 EKGERMGCPA595 GCPREMYDLM605 NLCWTYDVEN615 RPGFAAVELR 625 LRNYYYD
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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:519 or .A:523 or .A:524 or .A:526 or .A:527 or .A:548 or .A:549 or .A:550; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 3SRV Crystal structure of spleen tyrosine kinase (SYK) in complex with a diaminopyrimidine carboxamide inhibitor | ||||||
| Method | X-ray diffraction | Resolution | 1.95 Å | Mutation | No | [2] |
| PDB Sequence |
YLDRKLLTLE
373 DKELGNFGTV385 KKGYYQMKKV395 VKTVAVKILK405 ALKDELLAEA421 NVMQQLDNPY 431 IVRMIGICEA441 ESWMLVMEMA451 ELGPLNKYLQ461 QNRHVKDKNI471 IELVHQVSMG 481 MKYLEESNFV491 HRDLAARNVL501 LVTQHYAKIS511 DFGLSKALRA521 DENYKAQTHG 532 KWPVKWYAPE542 CINYYKFSSK552 SDVWSFGVLM562 WEAFSYGQKP572 YRGMKGSEVT 582 AMLEKGERMG592 CPAGCPREMY602 DLMNLCWTYD612 VENRPGFAAV622 ELRLRNYYYD 632 VV
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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:519 or .A:523 or .A:524 or .A:526 or .A:527 or .A:548 or .A:549 or .A:550; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 5LMB HUMAN SPLEEN TYROSINE KINASE KINASE DOMAIN IN COMPLEX WITH AZANAPHTHYRIDINE INHIBITOR | ||||||
| Method | X-ray diffraction | Resolution | 1.95 Å | Mutation | No | [4] |
| PDB Sequence |
YLDRKLLTLE
373 DKELGSGNFG383 TVKKGYYQMK393 KVVKTVAVKI403 LPALKDELLA419 EANVMQQLDN 429 PYIVRMIGIC439 EAESWMLVME449 MAELGPLNKY459 LQQNRHVKDK469 NIIELVHQVS 479 MGMKYLEESN489 FVHRDLAARN499 VLLVTQHYAK509 ISDFGLSKAL519 RADENYKAQT 530 HGKWPVKWYA540 PECINYYKFS550 SKSDVWSFGV560 LMWEAFSYGQ570 KPYRGMKGSE 580 VTAMLEKGER590 MGCPAGCPRE600 MYDLMNLCWT610 YDVENRPGFA620 AVELRLRNYY 630 YDVV
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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:519 or .A:523 or .A:524 or .A:526 or .A:527 or .A:548 or .A:549 or .A:550; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 6HM7 CRYSTAL STRUCTURE OF SPLEEN TYROSINE KINASE (SYK) IN COMPLEX WITH A 2-(PHENOXYMETHYL)PYRIDINE INHIBITOR | ||||||
| Method | X-ray diffraction | Resolution | 1.64 Å | Mutation | No | [5] |
| PDB Sequence |
VYLDRKLLTL
372 EDKELGSGNF382 GTVKKGYYQM392 KKVVKTVAVK402 ILKNEANDPA412 LKDELLAEAN 422 VMQQLDNPYI432 VRMIGICEAE442 SWMLVMEMAE452 LGPLNKYLQQ462 NRHVKDKNII 472 ELVHQVSMGM482 KYLEESNFVH492 RDLAARNVLL502 VTQHYAKISD512 FGLSKALRAD 522 ENYKAQTWPV536 KWYAPECINY546 YKFSSKSDVW556 SFGVLMWEAF566 SYGQKPYRGM 576 KGSEVTAMLE586 KGERMGCPAG596 CPREMYDLMN606 LCWTYDVENR616 PGFAAVELRL 626 RNYYYDV
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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:519 or .A:523 or .A:524 or .A:526 or .A:527 or .A:548 or .A:549 or .A:550; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 6HM6 CRYSTAL STRUCTURE OF SPLEEN TYROSINE KINASE (SYK) IN COMPLEX WITH A 2-(PYRIDINYLOXYMETHYL)PYRIDINE INHIBITOR | ||||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | No | [5] |
| PDB Sequence |
YLDRKLLTLE
373 DKELGSGNFG383 TVKKGYYQMK394 VVKTVAVKIL404 DPALKDELLA419 EANVMQQLDN 429 PYIVRMIGIC439 EAESWMLVME449 MAELGPLNKY459 LQQNRHVKDK469 NIIELVHQVS 479 MGMKYLEESN489 FVHRDLAARN499 VLLVTQHYAK509 ISDFGLSKAL519 RADENYKAQG 532 KWPVKWYAPE542 CINYYKFSSK552 SDVWSFGVLM562 WEAFSYGQKP572 YRGMKGSEVT 582 AMLEKGERMG592 CPAGCPREMY602 DLMNLCWTYD612 VENRPGFAAV622 ELRLRNYYYD 632
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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:519 or .A:523 or .A:524 or .A:526 or .A:527 or .A:548 or .A:549 or .A:550; 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 | Imidazotriazines: Spleen Tyrosine Kinase (Syk) Inhibitors Identified by Free-Energy Perturbation (FEP). ChemMedChem. 2016 Jan 19;11(2):217-33. | ||||
| REF 2 | Discovery of GSK143, a highly potent, selective and orally efficacious spleen tyrosine kinase inhibitor. Bioorg Med Chem Lett. 2011 Oct 15;21(20):6188-94. | ||||
| REF 3 | THE KINASE DOMAIN OF HUMAN SPLEEN TYROSINE (SYK) IN COMPLEX WITH GTC000250 | ||||
| REF 4 | Optimisation of a novel series of potent and orally bioavailable azanaphthyridine SYK inhibitors. Bioorg Med Chem Lett. 2016 Oct 1;26(19):4606-4612. | ||||
| REF 5 | Discovery of potent and selective Spleen Tyrosine Kinase inhibitors for the topical treatment of inflammatory skin disease. Bioorg Med Chem Lett. 2018 Nov 15;28(21):3458-62. | ||||
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