Serine/threonine protein kinase

From Proteopedia

Revision as of 11:55, 5 January 2014

spinqualitylabelsall models Crystal Structure of Glycogen Synthase Kinase 3ß bound to Anticancer Ruthenium Complex Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image Serine/threonine protein kinase 1 (Chk1) phosphorylates cdc25A, cdc25B and cdc25C. Upon phosphorylation, cdc25 binds adaptor protein and the cell is prevented from entering mitosis. Chk2 (Checkpoint kinase 2) phosphorylates cdc25C at Ser-216. Chk6 called also Aurora A is critical for the formation of mitotic spindles during cellular mitosis. Chk6 is phosphorylated at residues Thr287 and Thr288. Chk13 (Polo-like kinase 1 or Plk1) functions during the M phase of the cell cycle including the regulation of centrosome maturation and spindle assembly. Chk13 binds and phosphorylates proteins which are already phosphorylated on a motif recognized by its POLO-box domain (Pbd) at the C terminal. Human Chk13 contains catalytic domain (residues 13-345) and POLO-box domain (residues 345-603). Glycogen synthase kinase 3 (GSK-3) is a serine/threonine protein kinase. GSK-3 is active in a number of intracellular signaling pathways. GSK-3 regulates glycogen synthase as well as other proteins. GSK-3 inhibition is studied as a therapeutic target in diseases like Alzheimer, diabetes, bipolar disorder and some cancers. B-Raf is related to retroviral oncogenes and participates in cellular signal transduction. B-Raf domains include the kinase domain - residues 444-721 and Ras-binding domain - residues 153-237. Mutated B-Raf was found in some human cancers. See more in B-RAF with PLX4032. c-Raf is part of the MAPK pathway. c-Raf domains include the kinase domain - residues 323-618, cysteine-rich domain – residues 136-187 and Ras-binding domain - residues 51-132. Mutations of c-Raf are possible causes of Noonan syndrome. For details on c-Raf see Molecular Playground/C-Raf. For details on Snf1-related kinase see ABA-regulated SNRK2 Protein Kinase. Structure of Anticancer Ruthenium Half-Sandwich Complex Bound to Glycogen Synthase Kinase 3ß [1]         A crystal structure of an bound to the protein kinase glycogen synthase kinase 3ß (GSK-3ß) has been determined and reveals that the inhibitor binds to the via an induced fit mechanism utlizing several and . Importantly, the metal is not involved in any direct interaction with the protein kinase but fulfills a purely structural role. The unique, bulky molecular structure of the half-sandwich complex with the CO-ligand oriented perpendicular to the pyridocarbazole heterocycle allows the complex to stretch the whole distance and to interact tightly with . Although this complex is a conventional ATP-competitive binder, the unique shape of the complex allows novel interactions with the glycine-rich loop which are crucial for binding potency and selectivity. It can be hypothesized that coordination spheres which present other ligands towards the glycine-rich loop might display completely different protein kinase selectivities.

3D structures of serine/threonine protein kinase

Updated on 05-January-2014

Chk1

1nvq, 1nvr – hChk1 kinase domain+ peptide + saurosporine – human

1nvs, 1zys - hChk1 kinase domain + peptide + inhibitor

2cgu, 2cgv, 2cgw, 2cgx, 2c3j, 2c3k, 2c3l, 2br1, 2brb, 2brg, 2brh, 2brm, 2brn, 2bro, 2ayp, 2gdo, 2ghg, 2hog, 2ywp, 2hxl, 2hxq, 2hy0, 2r0u, 2e9n, 2e9o, 2e9p, 2e9u, 2e9v, 2qhm, 2qhn, 3f9n, 2wmq, 2wmr, 2wms, 2wmt, 2wmu, 2wmv, 2wmx, 3jvr, 3jvs, 2xey, 2xf0, 2xez, 2x8d, 2x8e, 2x8i, 3ot3, 3ot8, 3pa3, 3pa4, 3pa5, 3nlb - hChk1 kinase domain + inhibitor

Chk2

1gxc – hChk2 phosphothreonine-binding domain + phosphopeptide

2cn5 – hChk2 kinase domain + ADP

2cn8 – hChk2 kinase domain + inhibitor

2w0j, 2w7x, 2wtc, 2wtd, 2xbj, 2xm8, 2xm9, 2yiq, 2yir, 2yit - hChk2 kinase domain + inhibitor

3i6u, 3i6w – hChk2 residues 84-502 (mutant)

Chk6

1muo, 1mq4 – hChk6 kinase domain
1ol6 – hChk6 kinase domain (mutant) + ATP
2wqe – hChk6 kinase domain (mutant) + ADP
2c6d – hChk6 kinase domain (mutant) + ADPNP
2dwb – hChk6 kinase domain + AMPPNP
3daj, 3d14, 3dj5, 3dj6, 3dj7, 3d15, 3d2i, 3d2k – Chk6 kinase domain (mutant) + inhibitor - mouse
2j4z, 2j50, 2np8, 3efw, 2x81, 2x6d, 2x6e, 3myg, 3vap, 4b0g – hChk6 kinase domain + inhibitor
2bmc, 2c6e, 3coh, 3h0y, 3h0z, 3h10, 3fdn, 2wtw, 3lau, 3nrm, 2xne, 2xng, 2xru, 3k5u, 3m11, 3p9j, 3r21, 3r22, 3qbn, 3unz, 3uo4, 3uo5, 3uo6, 3uod, 3uoh, 3uoj, 3uok, 3uol, 3up2, 3up7, 4dhf, 4dea, 4deb, 4ded, 4dee – hChk6 kinase domain (mutant) + inhibitor

Chk6 with phosphorylated Thr 287, Thr288

1ol5, 1ol7 – hChk6 kinase domain + PThr + ADP
2w1c, 2w1d, 2w1e, 2w1f, 2w1g – hChk6 kinase domain + PThr + inhibitor
2wtv – hChk6 kinase domain (mutant) + PThr + inhibitor
3e5a, 3ha6 – hChk6 kinase domain + PThr + inhibitor + targeting protein for XKLP2

Chk13

Chk13 POLO-box domain (Pdb)

1q4o, 2ogq, 3hih, 3p2w, 4h5x – hChk13 Pbd

Chk13 Pbd complex with polypeptide

1umw, 2ojx, 3bzi, 3c5l, 3rq7, 4dfw – hChk13 Pbd + peptide
3hik, 3fvh, 3p2z, 3p34, 3p35, 3p36, 3p37, 3q1i, 4e67, 4e9c, 4e9d, 4hab, 4hy2 – hChk13 Pbd + phosphopeptide
1q4k – hChk13 Pbd (mutant) + phosphopeptide
2v5q – hChk13 Pbd + design ankyrin repeat protein

Chk13 Pbd complex with small molecule inhibitor

4h71, 4hco – hChk13 Pbd + inhibitor
2rku – hChk13 Pbd (mutant) + inhibitor
3db6, 3db8, 3dbc, 3dbd, 3dbe, 3dbf – zfChk13 Pbd (mutant) + inhibitor – zebra fish

Chk13 catalytic domain

2owb – hChk13 catalytic domain
2ou7 – hChk13 catalytic domain + AMPPNP
3d5w – zfChk13 catalytic domain + ADP
3kb7, 2yac, 3thb, 4a4l, 4a4o – hChk13 catalytic domain + inhibitor
3fc2 – hChk13 catalytic domain (mutant) + inhibitor
3d5x – zfChk13 catalytic domain (mutant) + wortmannin

Rac-β hChk

1gzk, 1gzn, 1gzo – Rac-β hChk kinase domain
1p6s - Rac-β hChk pleckstrin homology domain - NMR
1o6k - Rac-β hChk kinase domain + GSK3 peptide + AMPPNP
1o6l - Rac-β hChk kinase domain (mutant) + GSK3 peptide + AMPPNP

B-Raf

1uwh, 3c4c – hB-Raf kinase domain + anticancer drug
1uwj – hB-Raf kinase domain (mutant) + anticancer drug
2fb8 – hB-Raf kinase domain + inhibitor
3d4q, 3ii5, 3psd, 3skc, 3tv6, 4g9c – hB-Raf kinase domain + pyrazole inhibitor
4jvg – hB-Raf kinase domain (mutant) + pyrazole inhibitor
4ksp, 4ksq – hB-Raf kinase domain + benzothiazole inhibitor
3psb, 3ppj, 3ppk, 3prf, 3pri, 3tv4, 4dbn, 4e4x, 4mbj – hB-Raf kinase domain + pyridine inhibitor
4ehe – hB-Raf kinase domain + pyrimidine inhibitor
4ehg – hB-Raf kinase domain (mutant) + pyrimidine inhibitor
4fk3 – hB-Raf kinase domain (mutant) + pyridine inhibitor
3q4c – hB-Raf kinase domain + organometallic inhibitor
3q96 – hB-Raf kinase domain + naphthalene inhibitor
3e26, 4h58 – hB-Raf kinase domain + quinoline inhibitor
3idp, 4g9r – hB-Raf kinase domain (mutant) + quinoline inhibitor
2l05 – hB-Raf RAS-binding domain - NMR
3ny5 – hB-Raf RAS-binding domain

c-Raf

1rfa – hc-Raf RAS-binding domain - NMR
1rrb – c-Raf RAS-binding domain – NMR - rat
1faq, 1far – hc-Raf cysteine-rich domain - NMR
3omv – hc-Raf kinase domain

c-Raf complex with protein

1c1y – hc-Raf RAS-binding domain + RAP1A
3kuc – hc-Raf RAS-binding domain (mutant) + RAP1A
1gua – hc-Raf RAS-binding domain + RAP1A + GPPNHP
4g0n, 4g3x – hc-Raf RAS-binding domain + GTPase Hras
3kud – hc-Raf RAS-binding domain (mutant) + GTPase Hras

Snf1-related Chk

3uc4 – AtChk Srk2E kinase domain (mutant) – Arabidopsis thaliana
3ujg – AtChk Srk2E kinase domain (mutant) + protein phosphatase 2C

Various Chk

1c1y – hChk proto oncogene kinase domain + Ras-related protein Rap
2xiy, 2xiz, 2xj0 - hChk proto oncogene Pim-1 kinase domain
1u5q, 1u5r – rChk Tao2 kinase domain – rat
2cos – Chk Lats2 – mouse – NMR
2xik – hChk 25
3hgk – Chk Pto + effector protein AVRPTOB – Currant tomato
3ori, 3ork, 3orl, 3orm, 3oro, 3orp, 3ort - MtChk kinase domain (mutant) – Mycobacterium tuberculosis
3ouv - MtChk extracellular domain

References

1. ↑ Atilla-Gokcumen GE, Di Costanzo L, Meggers E. Structure of anticancer ruthenium half-sandwich complex bound to glycogen synthase kinase 3beta. J Biol Inorg Chem. 2010 Sep 7. PMID:20821241 doi:10.1007/s00775-010-0699-x