Tyrosine kinase
From Proteopedia
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| - | + | <StructureSection load='3ac1' size='450' side='right' scene='' caption=''> | |
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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.<br /> | '''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.<br /> | ||
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For references see [[Treatments:TYKI References]]. | For references see [[Treatments:TYKI References]]. | ||
| + | === Traditional Chinese medicine as dual guardians against hypertension and cancer? <ref>DOI 10.1080/07391102.2012.680030</ref> === | ||
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| + | <scene name='Journal:JBSD:14/Cv/2'>Src kinase</scene> 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 <scene name='Journal:JBSD:14/Cv/3'>smaller amino-terminal lobe</scene> (<span style="color:violet;background-color:black;font-weight:bold;">residues 270–340; colored in violet</span>) which binds adenosine triphosphate (ATP) and a <scene name='Journal:JBSD:14/Cv/5'>larger carboxyl-terminal lobe</scene> (<span style="color:lime;background-color:black;font-weight:bold;">residues 345–523; colored in green</span>) 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, <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 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. | ||
| + | </StructureSection> | ||
__NOTOC__ | __NOTOC__ | ||
==3D structures of tyrosine kinase== | ==3D structures of tyrosine kinase== | ||
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[[3sxr]] - hTK Bmx kinase domain (mutant) + dasatinib<br /> | [[3sxr]] - hTK Bmx kinase domain (mutant) + dasatinib<br /> | ||
[[3sxs]] - hTK Bmx kinase domain (mutant) + inhibitor<br /> | [[3sxs]] - hTK Bmx kinase domain (mutant) + inhibitor<br /> | ||
| - | + | <references/> | |
[[Category:Topic Page]] | [[Category:Topic Page]] | ||
Revision as of 10:56, 20 February 2014
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3D structures of tyrosine kinase
Updated on 20-February-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
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
