Tyrosine kinase

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Revision as of 09:50, 21 July 2014

Human Src tyrosine kinase kinase domain complex with inhibitor (PDB code 2bdf).

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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. Staurosporine inhibits TK and prevents ATP binding to it.

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.

1 3D structures of tyrosine kinase

3D structures of tyrosine kinase

Updated on 21-July-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
1zbj - hTK Fyn SH3 domain – NMR
1g83 - hTK Fyn SH2+SH3 domains (mutant)

Fyn complex

1fyn - hTK Fyn SH3 domain + peptide
1nyf, 1nyg - hTK Fyn SH3 domain + peptide – NMR
1efn, 1avz - hTK Fyn SH3 domain + HIV Nef protein
1m27 - hTK Fyn SH3 domain + SH2 domain protein 1A + SLAM peptide
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
2dq7 – hTK kinase domain + staurosporine

Abelson tyrosine kinase

Abl1 SH2 domain residues 120-220

1ab2 - hTK SH2 domain – NMR
3uyo, 3t04, 3k2m - hTK SH2 domain + monobody

Abl1 SH3 domain residues 60-121

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
4jjb, 4jjc, 4jjd - hTK abl SH3 domain
4j9b, 3egu, 3eg2, 3eg3, 3eg0, 3eg1 - hTK abl SH3 domain (mutant)
4j9c, 4j9e, 4j9i - hTK abl SH3 domain (mutant) + p17 peptide
4j9d, 4j9f - hTK abl SH3 domain (mutant) + p0 peptide
4j9g, 4j9h - hTK abl SH3 domain (mutant) + p7 peptide

Abl1 SH3-SH2 domain

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

Abl1 kinase domain residues 229-512

2g2h - hTK kinase domain (mutant)
1opj, 1opk - mTK kinase domain
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}

Abl1 F-actin binding domain residues 1007-1130

1zzp - hTK abl F-actin binding domain – NMR

Abl2 SH2 domain residues 165-273

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

Abl2 kinase domain residues 279-546

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

Abl2 C-terminal residues 1058-1182

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

3eac - hTK
4f59, 3eaz - hTK (mutant)
1f2f - cTK (mutant)
1spr - RsvTK + phosphate – Rous sarcoma virus
1kc2, 1sps - RsvTK + peptide
1sha, 1shb - RsvTK + phosphopeptide
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, 4jz3, 4jz4 - cTK
4le9 - cTK (mutant)
4hxj, 1prl - cTK + peptide
1prm, 1rlp, 1rlq, 1nlo, 1nlp - cTK + peptide - NMR
4hvu, 4hvv, 4hvw - cTK (mutant) + peptide
1jeg – TK + protein-tyrosine phosphatase peptide – mouse

Src tyrosine kinase kinase domain residues 253-535

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
1byg – hTK + staurosporine
4mxo – hTK + cancer drug
4mxx, 4mxy, 4mxz – hTK (mutant) + cancer drug
3d7t, 3d7u – cTK + Csk
3dqw, 3dqx - cTK (mutant) + ATP

Src tyrosine kinase C terminal domain

1yi6 - hTK
1k9a – rTK – rat

Src tyrosine kinase SH2+SH3+kinase domains residues 85-535

1ksw – hTK (mutant)+ ADP derivative
1y57 – hTK + inhibitor
1y57 – hTK (mutant) + inhibitor

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
1q68 - hTK Lck residues 6-34 (mutant) + CD4 peptide – NMR
1q69 - hTK Lck residues 6-34 (mutant) + CD8 – NMR

Syk - spleen tyrosine kinase

1xba – Syk kinase domain

Syk complex

1xbb - Syk kinase domain + Gleevec
1xbc - Syk kinase domain + staurosporine
3emg, 3fqe, 3fqh, 3fqs, 3srv, 4dfl, 4dfn, 3vf8, 3vf9, 3tub, 3tuc, 3tud, 4f4p, 4fyn, 4fyo, 4fz6, 4fz7, 4gfg, 4i0r, 4i0s, 4i0t, 4puz, 4pv0 - Syk kinase domain + inhibitor
4px6 - Syk kinase domain (mutant) + 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
4l7s, 4m0y, 4m0z, 4m12, 4m13, 4m14, 4m15, 4mf0, 4mf1 - hTK Itk kinase domain + inhibitor

Zap tyrosine kinase

4k2r – hTK Zap
2ozo - hTK Zap (mutant)
1m61 - hTK Zap SH2 domain

Zap complex

2oq1 - hTK Zap SH2 domain + peptide
1u59 - hTK Zap kinase domain + staurosporine

2β tyrosine kinase

3cc6, 3fzo - hTK Pyk2 kinase domain
3gm2 - hTK Pyk2 FAT domain
3gm3 - hTK Pyk2 FAT domain (mutant)
4eku – hTK Pyk2 FERM domain
2lk4 - hTK Pyk2 FAT domain – NMR

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

CapAB tyrosine kinase

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

Fer tyrosine kinase

2kk6 - hTK Fer SH2 domain – NMR

Ptk6 tyrosine kinase

1rja - hTK Ptk6 SH2 domain – NMR
2kgt - hTK Ptk6 SH3 domain – NMR

Lyn tyrosine kinase

1w1f - hTK Lyn SH3 domain – NMR
1wa7 - hTK Lyn SH3 domain + peptide – NMR
3a4o - hTK Lyn residues 233-512 + staurosporine
2zv7 - mTK Lyn kinase domain
2zv8 - mTK Lyn kinase domain + AMPPNP
2zv9 - mTK Lyn kinase domain + PP2
2zva - mTK Lyn kinase domain + cancer drug

Txk tyrosine kinase

2dm0 - hTK Txk SH2 domain – NMR

Yes tyrosine kinase

2hda - hTK Yes SH3 domain

Tec tyrosine kinase

2lul - hTK Tec PH domain - NMR

Fes/Fps tyrosine kinase

1wqu, 2dcr - hTK Fes SH2 domain - NMR
3bkb - hTK Fes SH2+kinase domain - NMR
4dyl - hTK Fes F-Bar domain
3cbl - hTK Fes SH2+kinase domain + peptide
3cd3 - hTK Fes SH2+kinase domain + peptide + staurosporine
4e93 - hTK TFes + inhibitor

Etk tyrosine kinase

3cio - EcTK Etk kinase domain – Escherichia coli

Wzc tyrosine kinase

3la6 - EcTK Wzc kinase domain

Ros tyrosine kinase

3zbf - hTK Ros kinase domain + cancer drug

Tyk tyrosine kinase

3lxn, 3lxp, 3nyx, 3nz0, 4e1z, 4e20, 4gfo, 4gih, 4gii, 4gj2, 4gj3 - hTK Tyk2 kinase domain (mutant) + inhibitor
4gvj - hTK Tyk2 kinase domain (mutant) + ADP
4po6 - hTK Tyk2 SH2+FERM domains + IFNAR1 peptide

Kit tyrosine kinase

2ec8 - hNTPK Kit extracellular domain
3g0e, 3g0f - hNTPK Kit kinase domain (mutant) + cancer drug
2e9w, 2o26 - hNTPK Kit extracellular domain + stem cell factor

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
4lud, 4lue - hTK Hck SH2+SH3+kinase domain (mutant) + fluorescent compound
4orz - hTK Hck SH3 domain (mutant) + NEF + single domain antibody

Receptor tyrosine kinases - RTK

Bruton’s tyrosine kinase

2z0p - hTK Btk PH domain
1btk – hTK Btk PH domain (mutant)
3p08, 1k2p - 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, 4nwm - hTK Btk kinase domain + inhibitor
3k54, 3t9t, 4ot5, 4ot6, 4otq, 4otr - 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 kinase domain

Mer complex

3brb - hTK Mer kinase domain + ADP
3bpr, 3tcp, 4m3q, 4mh7, 4mha - hTK Mer kinase 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

ErbB tyrosine kinase

See Epidermal Growth Factor Receptor

Musk tyrosine kinase

3hkl - rTK Musk Fz-Crd domain

↑ 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 19: / Line 19: @@
 	In this ''in vivo'' study, <scene name='Journal:JBSD:14/Cv/7'>Angeliferulate</scene> and <scene name='Journal:JBSD:14/Cv/8'>HMID</scene> 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 af&#64257;nity 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.
 </StructureSection>
-__NOTOC__
 ==3D structures of tyrosine kinase==