Tyrosine kinase

From Proteopedia

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Revision as of 10:46, 9 March 2014

Tyrosine kinase (TK) transfers a phosphate group from ATP to tyrosine residues of proteins. Mutated TK can cause unregulated growth of the cell and their inhibitors can be effective cancer treatment. TKs are classified as receptor-TK which are membrane-attached and cytoplasmic non-receptor TKs. TK contains, starting from the N-terminal, SH4 – a membrane attachment domain; SH3 and SH2 domains which are a sequence-specific phosphotyrosine binding domains with roles in protein-protein interactions and the SH1 catalytic kinase domain.

For Abelson tyrosine kinase see:

Bcr-Abl and Imatinib (STI571 or Gleevec).

For Src tyrosine kinase see:

Traditional Chinese medicine as dual guardians against hypertension and cancer? ^[1]

functions as a signal protein and is implicated in various diseases. The carboxyl terminal of Src kinase is important in regulating conformation and activity of Src. Src protein is locked as an inward folding conformation through binding between the phosphorylated Tyr527 and the SH2 domain under normal inactive conditions. Src is activated when dephosphorylation of Tyr527 and phosphorylation of Tyr419 occurs. From N-terminal to C-terminal, Src is composed of a (residues 270–340; colored in violet) which binds adenosine triphosphate (ATP) and a (residues 345–523; colored in green) which binds with substrates. The ATP binding site is also partially located in the larger lobe. By regulating the alpha-helix structure, the large lobe can move toward or away from the small lobe, opening or closing the cleft between the two lobes. The Src catalytic site is located within the cleft. An open conformation allows the entrance of ATP into the cleft and exit of adenosine diphosphate (ADP) from the cleft. Drugs that can either interact with the residues (404–432) on the activation loop or inhibit the activation loop from moving away and opening the cleft as a result of Tyr419 phosphorylation can effectively inhibit Src activity. In this in vivo study, and have multiple stable interactions with the two Src cleft loops while simultaneously interacting with Asp407, hindering the activation loop from activation. Considering the aforementioned interactions with Src and high afﬁnity with EGFR, HER2, and HSP90, we suggest that Angeliferulate and HMID which both originate from the TCM Angelica sinensis may have potential as multi-targeting drug leads.

3D structures of tyrosine kinase

Updated on 09-March-2014

Non-receptor tyrosine kinases - nRTK

Fyn tyrosine kinase

1shf, 3ua6 – hTK Fyn SH3 domain – human
3h0f, 3h0h, 3h0i - hTK Fyn SH3 domain (mutant)
2l2p, 2lp5 - cTK Fyn SH3 domain (mutant)- chicken - NMR
3uf4 – mTK Fyn SH3-SH2 domain – mouse

Fyn complex

1fyn - hTK Fyn SH3 domain + peptide
1efn, 1avz - hTK Fyn SH3 domain + HIV Nef protein
4d8d - hTK Fyn SH3 domain (mutant) + HIV Nef protein
3ua7 – hTK Fyn SH3 domain + hepatitis virus peptide
4eik - hTK Fyn SH3 domain + VSL12 peptide
1aot, 1aou - hTK Fyn SH2 domain + phosphopeptide - NMR

Abelson tyrosine kinase

Abl1 SH2 domain

1ab2 - hTK SH2 domain – NMR
3egu, 3eg2, 3eg3, 3eg0, 3eg1 - hTK SH2 domain (mutant)
3uyo, 3t04, 3k2m - hTK SH2 domain + monobody

Abl1 SH3 domain

1ju5 - hTK SH3 domain (mutant) + CRK SH2 domain + phosphopeptide - NMR
1awo - hTK SH3 domain + phosphopeptide – NMR
1bbz - hTK SH3 domain + peptide
2o88 - hTK SH3 domain (mutant} + peptide
1abo - mTK SH3 domain + peptide
1abq - mTK SH3 domain

Abl1 SH3-SH2 domain

2abl - hTK SH3-SH2 domain
2fo0 - hTK SH3-SH2 domain (mutant)

Abl1 kinase domain

2g2h - hTK kinase domain (mutant)
1opj, 1opk - mTK kinase domain
2g1t - hTK kinase domain + peptide
2g2i, 2g2f - hTK kinase domain (mutant) + peptide
3ue4, 3cs9, 2hzi, 2hz4, 2hz0, 2hyy, 2gqg - hTK kinase domain + cancer drug
2f4j - hTK kinase domain (mutant) + cancer drug
3qrk, 3qri, 3qrj, 2v7a, 2e2b, 2hiw - hTK kinase domain + inhibitor
1fpu, 1m52, 2qoh, 3kf4, 3kfa - mTK kinase domain + inhibitor
2z60, 3dk3, 3dk6, 3dk7 - mTK kinase domain (mutant) + inhibitor
1iep, 2hzn, 3k5v, 3ms9, 3mss, 3oxz - mTK kinase domain + cancer drug
3ik3, 3oy3 - mTK kinase domain (mutant) + cancer drug

Abl1 SH3-SH2-kinase domain

1opl - hTK SH3-SH2-kinase domain (mutant}

Abl2 SH2 domain

4eih - hTK SH2 domain
2ecd - hTK SH2 domain – NMR

Abl2 kinase domain

3gvu - hTK kinase domain + Gleevec
3hmi - hTK kinase domain + inhibitor
2xyn - hTK kinase domain + cancer drug

Abl2 C-terminal

2kk1 – hTK C terminal – NMR

Anaplastic lymphoma kinase (Alk)

2xb7, 2xba, 3aox - hTK kinase domain + inhibitor
4dce, 4fob, 4foc, 4fod, 4fny, 4fnz, 4joa - hTK kinase domain (mutant) + inhibitor
2xp2 - hTK kinase domain + cancer drug
2yfx, 4anq, 4ans - hTK kinase domain (mutant) + cancer drug
3l9p, 3lcs, 3lct, 2yhv, 2yjr, 2yjs, 4fnw, 4fnx, 4anl - hTK kinase domain (mutant)

Csk tyrosine kinase

3eac - hTK SH2 domain
3eaz - hTK SH2 domain (mutant)
2rsy - hTK SH2 domain + CBP phosphopeptide - NMR
1csk - hTK SH3 domain
1jeg - hTK SH3 domain + tyrosine phosphatase peptide - NMR
1byg - hTK kinase domain + staurosporine
3d7t, 3d7u - hTK kinase domain (mutant) + C-Src
1k9a - TK C terminal - rat

Jak tyrosine kinase

See Janus kinase

p55-blk tyrosine kinase

1blj, 1blk - mTK p55-blk SH2 domain – NMR

Src tyrosine kinase

Src tyrosine kinase SH2 domain

4f59 - hTK (mutant)
1f2f - cTK (mutant)
1spr - RsvTK + phosphate – Rous sarcoma virus
1kc2 - RsvTK + peptide
1shd - cTK + TRKA receptor
4f5b - hTK (mutant) + phosphotyrosine
4f5a - hTK (mutant) + phosphate
1o4c - hTK + phosphate
1o41, 1o42, 1o43, 1o44, 1o45, 1o46, 1o47, 1o48, 1o49 1o4a, 1o4b, 1o4d 1o4e, 1o4f, 1o4g 1o4h, 1o4i, 1o4j 1o4k, 1o4l, 1o4m 1o4n, 1o4o, 1o4p 1o4q, 1o4r - hTK + inhibitor
1hcs, 1hct - hTK + peptide - NMR
1a07, 1a08, 1a09, 1a1a, 1a1b, 1a1c, 1a1e - hTK + peptide
1f1w - cTK (mutant) + peptide
1p13 - cTK + peptide

Src tyrosine kinase SH3 domain

1srl, 1srm - cTK – NMR
3fj5 - cTK
4hxj, 1prl - cTK + peptide
1prm, 1rlp, 1rlq, 1nlo, 1nlp - cTK + peptide - NMR
4hvu, 4hvv, 4hvw - cTK (mutant) + peptide

Src tyrosine kinase kinase domain

3of0, 2qi8 - cTK (mutant)
1yoj - hTK (mutant)
3tz7, 3tz8, 3tz9, 4dgg – cTK (mutant) + pyrazolin derivative
4fic, 3uqg, 3uqf, 3u51, 3u4w, 4agw, 3qlg, 3qlf, 3g6g, 3el8, 3f6x, 2hwo, 2hwp, 2oiq, 3en4, 3en5, 3en6, 3en7, 3el7 – cTK + inhibitor
4lgg, 4lgh, 3svv, 3oez, 3lok, 3g5d, 3f3w, 3f3v, 3geq, 3g6h, 3f3t, 3f3u, 2qlq, 2qq7, 4lgg, 4lgh – cTK (mutant) + inhibitor
1yol, 1yom – hTK (mutant) + inhibitor
2bdf, 2bdj – hTK + inhibitor
3d7t, 3d7u – cTK + Csk
3dqw, 3dqx - cTK (mutant) + ATP

Src tyrosine kinase C terminal domain

1yi6 - hTK

Src tyrosine kinase SH2+SH3+kinase domains

1ksw – hTK (mutant)+ ADP derivative

Src tyrosine kinase SH2+SH3+kinase+C terminal domains

1fmk – hTK
2ptk – cTK
2src – hTK + AMPPNP

Src tyrosine kinase N terminal+SH2+SH3+kinase domains

2h8h – hTK + inhibitor

Lymphocyte-specific tyrosine kinase Lck

1kik, 1h92 - hTK Lck SH3 domain – NMR
2iim - hTK Lck SH3 domain
4d8k, 1x27 - hTK Lck SH3-SH2 domain
3lck - hTK Lck kinase domain

Lck complex

1lcj, 1lkk, 1lkl - hTK Lck SH2 domain (mutant) + phosphopeptide
1cwd, 1cwe, 1ijr - hTK Lck SH2 domain + phosphopeptide
1bhf - hTK Lck SH2 domain + peptide inhibitor
1fbz - hTK Lck SH2 domain + inhibitor
1bhh - hTK Lck SH2 domain + T-lymphocyte-specific TK
1lck - hTK Lck SH3-SH2 domain (mutant) + phosphopeptide
1x27 - hTK Lck SH3-SH2 domain + peptide
1qpj - hTK Lck kinase domain + staurosporin
2of2, 2of4, 2ofu, 2ofv, 2og8, 3b2w, 3bym, 3bys, 3byu, 2zm1, 2zm4, 3byo, 2zyb, 3ac1, 3ac2, 3ac3, 3ac4, 3ac5, 3ac8, 3acj, 3ack, 3kmm, 3ad4, 3ad5, 3ad6, 1qpc, 1qpd, 1qpe - hTK Lck kinase domain + inhibitor
3mpm - hTK Lck kinase domain (mutant) + inhibitor
4c3f - hTK Lck kinase domain (mutant) + chemotype
2pl0 - hTK Lck kinase domain + imatinib
3kxz - hTK Lck kinase domain + probe molecule

Syk - spleen tyrosine kinase

1xba – Syk kinase domain

Syk complex

1xbb - Syk kinase domain + Gleevec
1xbc - Syk kinase domain + staurosporin
3emg, 3fqe, 3fqh, 3fqs, 3srv, 4dfl, 4dfn, 3vf8, 3vf9, 3tub, 3tuc, 3tud, 4f4p, 4fyn, 4fyo, 4fz6, 4fz7, 4gfg - Syk kinase domain + inhibitor
1csy, 1csz - Syk SH2 domain + phosphopeptide – NMR
4fl1, 4fl2 - Syk kinase domain + ANP
4fl3 - Syk kinase domain (mutant) + ANP
1a81 – Syk tandem SH2 domain + T-cell surface peptide

Itk tyrosine kinase

1lui, 1luk, 1lum, 1lun – mTK Itk SH2 domain – NMR
3s9k – mTK Itk SH2 domain
2etz, 2eu0 – hTK Itk SH2 domain + phosphopeptide – NMR
1awj, 2rn8, 2rna – mTK Itk SH3 domain – NMR
2yuq, 2lmj – hTK Itk SH3 domain – NMR
2k79, 2k7a – mTK Itk SH2+SH3 domains – NMR
1sm2, 1snu, 1snx – hTK Itk kinase domain
3miy – hTK Itk kinase domain + cancer drug
3v5j, 3v5l, 3v8t, 3v8w – hTK Itk kinase domain + inhibitor
3mj1, 3mj2, 3qgw, 3qgy, 4hct, 4hcu, 4hcv, 4kio – hTK Itk kinase domain (mutant) + inhibitor
3t9t – hTK Itk kinase domain (mutant) + arthritis drug
2e6i – hTK Itk BTK motif – NMR

Zap tyrosine kinase

2ozo - hTK Zap (mutant)
1m61 - hTK Zap SH2 domain

Zap complex

2oq1 - hTK Zap SH2 domain + peptide
1u59 - hTK Zap catalytic domain + staurosporin

2β tyrosine kinase

3cc6, 3fzo - hTK Pyk2 kinase domain
3gm2 - hTK Pyk2 FAT domain
3gm3 - hTK Pyk2 FAT domain (mutant)

Pyk2 complex

3fzp - hTK Pyk2 kinase domain + ATPγS
3fzr, 3fzs, 3fzt, 3h3c, 3et7 - hTK Pyk2 kinase domain + inhibitor
3gm1 - hTK Pyk2 FAT domain + paxillin peptide
4h1j - hFAK2 kinase domain + pyrazole inhibitor
4h1m - hFAK2 kinase domain + indole inhibitor
3u3c, 3u3f – hFAK2 FAT domain (mutant) + paxillin LD2 motif
4eku – hFAK2 FERM domain

CapAB tyrosine kinase

3bfv - SaTK CapA1/CapB2 – Staphylococcus aureus
2ved - SaTK CapA1/CapB2 + Mg + ADP

Fer tyrosine kinase

2kk6 - hTK Fer SH2 domain – NMR

Hck tyrosine kinase

3hck - hTK SH2 domain - NMR
1bu1 - hTK SH3 domain
4hck, 5hck - hTK SH3 domain - NMR
2oj2, 2oi3 - hTK SH3 domain + peptide - NMR
3rbb, 3rea, 3reb - hTK SH3 domain (mutant) + HIV NEF
3nhn - hTK SH3-SH2-linker domain
2c0i, 2c0o, 2c0t - hTK SH3-SH2-SH1 domain + inhibitor
2hk5 - hTK kinase domain + inhibitor
1qcf, 3vry, 3vrz, 3vs0, 3vs1, 3vs2, 3vs3, 3vs4, 3vs5, 3vs6, 3vs7 - hTK SH3-SH2-kinase-tail domain + inhibitor
1ad5 - hTK SH3-SH2-kinase-tail domain + AMPPNP
2hck - hTK SH3-SH2-kinase-tail domain + quercetin

Receptor tyrosine kinases - RTK

Bruton’s tyrosine kinase

2z0p - hTK Btk PH domain
1btk – hTK Btk PH domain (mutant)
3p08 - hTK Btk kinase domain
1aww, 1awx, 1qly - hTK Btk SH3 domain – NMR
2ge9 - hTK Btk SH2 domain – NMR

Btk complex

1b55 - hTK Btk PH domain + inositol-tetrakisphosphate
1bwn - hTK Btk PH domain (mutant) + inositol-tetrakisphosphate
3gen, 3ocs, 3pix, 3piy, 3piz, 3pj1, 3pj2, 3pj3 - hTK Btk kinase domain + inhibitor
3k54, 3t9t - hTK Btk kinase domain (mutant) + inhibitor
3oct - hTK Btk kinase domain (mutant) + cancer drug

Fms tyrosine kinase

2i0v - hTK Fms kinase domain

Fms complex

2i0y, 2i1m - hTK Fms kinase domain + inhibitor
3dpk - hTK Fms kinase domain (mutant) + inhibitor
1flt – hTK Fms Igg-like domain + VEGF
1qty - hTK Fms domain 2 + VEGF

Mer tyrosine kinase

2dbj - hTK Mer FN2 domain – NMR
2p0c - hTK Mer catalytic domain

Mer complex

3brb - hTK Mer catalytic domain + ADP
3bpr - hTK Mer catalytic domain + inhibitor

Bone marrow tyrosine kinase

2ekx - hTK Bmx SH2 domain – NMR
2ys2 - hTK Bmx Btk motif – NMR

Bmx complex

3sxr - hTK Bmx kinase domain (mutant) + dasatinib
3sxs - hTK Bmx kinase domain (mutant) + inhibitor

↑ Tou WI, Chen CY. Traditional Chinese medicine as dual guardians against hypertension and cancer? J Biomol Struct Dyn. 2012 Jul;30(3):299-317. Epub 2012 Jun 12. PMID:22694277 doi:10.1080/07391102.2012.680030

Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky, Joel L. Sussman

Retrieved from "http://52.214.119.220/wiki/index.php/Tyrosine_kinase"

Category: Topic Page

@@ Line 253: / Line 253: @@
 [[3fzr]], [[3fzs]], [[3fzt]], [[3h3c]], [[3et7]] - hTK Pyk2 kinase domain + inhibitor<br />
 [[3gm1]] - hTK Pyk2 FAT domain + paxillin peptide<br />
+[[4h1j]] - hFAK2 kinase domain + pyrazole inhibitor<br />
+[[4h1m]] - hFAK2 kinase domain + indole inhibitor<br />
+[[3u3c]], [[3u3f]] – hFAK2 FAT domain (mutant) + paxillin LD2 motif<br />
+[[4eku]] – hFAK2 FERM domain<br />
 ===CapAB tyrosine kinase===

Tyrosine kinase

From Proteopedia

Revision as of 10:46, 9 March 2014

Traditional Chinese medicine as dual guardians against hypertension and cancer? ^[1]

3D structures of tyrosine kinase

Fyn tyrosine kinase

Abelson tyrosine kinase

Anaplastic lymphoma kinase (Alk)

Csk tyrosine kinase

Jak tyrosine kinase

p55-blk tyrosine kinase

Src tyrosine kinase

Lymphocyte-specific tyrosine kinase Lck

Syk - spleen tyrosine kinase

Itk tyrosine kinase

Zap tyrosine kinase

2β tyrosine kinase

CapAB tyrosine kinase

Fer tyrosine kinase

Hck tyrosine kinase

Bruton’s tyrosine kinase

Fms tyrosine kinase

Mer tyrosine kinase

Bone marrow tyrosine kinase

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Tyrosine kinase

From Proteopedia

Revision as of 10:46, 9 March 2014

Traditional Chinese medicine as dual guardians against hypertension and cancer? [1]

3D structures of tyrosine kinase

Fyn tyrosine kinase

Abelson tyrosine kinase

Anaplastic lymphoma kinase (Alk)

Csk tyrosine kinase

Jak tyrosine kinase

p55-blk tyrosine kinase

Src tyrosine kinase

Lymphocyte-specific tyrosine kinase Lck

Syk - spleen tyrosine kinase

Itk tyrosine kinase

Zap tyrosine kinase

2β tyrosine kinase

CapAB tyrosine kinase

Fer tyrosine kinase

Hck tyrosine kinase

Bruton’s tyrosine kinase

Fms tyrosine kinase

Mer tyrosine kinase

Bone marrow tyrosine kinase

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox

Traditional Chinese medicine as dual guardians against hypertension and cancer? ^[1]