Serine/threonine protein kinase

From Proteopedia

Revision as of 11:49, 30 December 2013

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. Mutated B-Raf was found in some human cancers. See more in B-RAF with PLX4032. 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 30-December-2013

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

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