Serine/threonine protein kinase

From Proteopedia

Revision as of 09:30, 20 August 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 ABA Signaling Pathway. 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 20-August-2014

Chk1

1ia8 – hChk1 – human
1zlt – hChk1 + hymenaldisine
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, 2wmw, 2ydi, 2ydj, 2ydk, 2yer, 2yex, 2ym3, 2ym4, 2ym5, 2ym6, 2ym7, 2ym8, 3tkh, 3tki, 3u9n, 4fsm, 4fsn, 4fsq, 4fsr, 4fst, 4fsu, 4fsw, 4fsy, 4fsz, 4ft0, 4ft3, 4ft5, 4ft7, 4ft9, 4fta, 4ftc, 4fti, 4ftj, 4ftk, 4ftl, 4ftm, 4ftn, 4fto, 4ftq, 4ftr, 4ftt, 4ftu, 4gh2, 4hyh, 4hyi, 4jik - hChk1 kinase domain + inhibitor
2jqi – yChk1 – yeast

Chk2 (Checkpoint kinase)

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, 2cn8, 2ycf, 2ycq, 2ycr, 2ycs, 2wti, 2wtj, 2xk9, 4a9r, 4a9s, 4a9t, 4bda, 4bdb, 4bdc, 4bdd, 4bde, 4bdf, 4bdg, 4bdh, 4bdi, 4bdj, 4bdk - hChk2 kinase domain + inhibitor

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

Chk3 (Mst2)

4hkd, 4l0n – hChk3 SARAH domain
4lg4 – hChk3 kinase domain
4lgd – hChk3 kinase domain + RASSF5 SARAH domain

Chk4 (Mst1)

2jo8 – hChk4 C terminal domain - NMR
3com – hChk4 kinase domain
4nr2 – hChk4 SARAH domain

Chk5 (Aurora kinase b)

4af3 – hChk5 + inhibitor

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

Chk10

2j7t, 4aot, 4equ – hChk10 kinase domain + inhibitor

Chk11

2wtk – hChk11 (mutant) + calcium-binding protein

Chk12 (Aurora kinase b-a)

2vgo, 2vgp, 2vrx, 3ztx, 4c2v – fChk12 + inner centromere protein A peptide + inhibitor - frog
4c2w – fChk12 + inner centromere protein A peptide + AMPPNP
4b8l, 4b8m – fChk12 (mutant) + inner centromere protein A peptide + inhibitor

Chk13 (Polo-like kinase Plk)

Plk1 Polo-box domain (Pdb)

1q4o, 2ogq, 3hih, 3p2w, 4h5x – Plk1 Pbd

Plk1 Pbd complex with polypeptide

1umw, 2ojx, 3bzi, 3c5l, 3rq7, 4dfw – Plk1 Pbd + peptide
3hik, 3fvh, 3p2z, 3p34, 3p35, 3p36, 3p37, 3q1i, 4e67, 4e9c, 4e9d, 4hab, 4hy2 – Plk1 Pbd + phosphopeptide
1q4k – Plk1 Pbd (mutant) + phosphopeptide
2v5q – Plk1 Pbd + design ankyrin repeat protein
4lkl – hChk Plk1 + PL-55
4lkm – hChk Plk1 + PL-74
4mlu – hChk Plk1 + peptide

Plk1 Pbd complex with small molecule inhibitor

4h71, 4hco – Plk1 Pbd + inhibitor
2rku – Plk1 Pbd (mutant) + inhibitor
3db6, 3db8, 3dbc, 3dbd, 3dbe, 3dbf – zfPlk1 Pbd (mutant) + inhibitor – zebra fish

Plk1 catalytic domain

2owb – Plk1 catalytic domain
2ou7 – Plk1 catalytic domain + AMPPNP
3d5w – zfPlk1 catalytic domain + ADP
3kb7, 2yac, 3thb, 4a4l, 4a4o – Plk1 catalytic domain + inhibitor
3fc2 – Plk1catalytic domain (mutant) + inhibitor
4j52, 4j53 – hChk Plk1 (mutant) + inhibitor
3d5x – zfPlk1 catalytic domain (mutant) + wortmannin

Plk2

4i5m, 4i5p, 4i6f, 4i6h – hChk Plk2 (mutant) + inhibitor

Plk3

4b6l, 4i6b – hChk Plk3 kinase domain + inhibitor

Chk15 (Aurora kinase a)

4bn1 – hChk15 (mutant)
4byi, 4byj, 4jai, 4jaj, 3w10, 3w16, 3w18, 3w2c – hChk15 kinase domain + inhibitor
4jbo, 4jbp, 4jbq – hChk15 kinase domain (mutant) + inhibitor

Chk16

2buj – hChk13 (mutant) + staurosporin

Chk17

3lm0 – hChk17B
3lm5 – hChk17B + quercetin

Chk24

3a7f, 3a7g, 3a7h, 3a7i, 3a7j, 3ckw – hChk24 kinase domain
3ckx – hChk24 kinase domain + staurosporin
3zhp – hChk24 kinase domain + calcium-binding protein

Chk25

2xik – hChk25
3w8h – hChk25 + programmed cell death protein 10

Chk32

4fr4 – hChk32A

Rac-α hChk

1h10, 1unq, 2uvm – hRac-α hChk pleckstrin homology domain + inositol tetrakisphosphate
1unp, 1unr – hRac-α hChk pleckstrin homology domain
2uzr, 2uzs – hRac-α hChk pleckstrin homology domain (mutant)
3o96, 4ejn - hRac-α hChk + inhibitor
4gv1 - hRac-α hChk kinase domain + inhibitor
4ekl - hRac-α hChk (mutant) + inhibitor
4ekk - hRac-α hChk (mutant) + glycogen synthase kinase-3 peptide + AMPPNP
3ow4, 3qkk, 3qkl - hRac-α hChk kinase domain (mutant) + GSK3 peptide + inhibitor
3qkm - hRac-α hChk kinase domain (mutant) + inhibitor

Rac-β hChk

1gzk, 1gzn, 1gzo, 1mrv, 1mry – Rac-β hChk kinase domain
1p6s - Rac-β hChk pleckstrin homology domain - NMR
1o6k - Rac-β hChk kinase domain + GSK3 peptide + AMPPNP
2jdo, 2jdr, 2uw9, 2x39, 3cqu, 3cqw - Rac-β hChk kinase domain + GSK3 peptide + inhibitor
3e87, 3e88, 3e8d - Rac-β hChk kinase domain (mutant) + GSK3 peptide + inhibitor<br / 1o6l - Rac-β hChk kinase domain (mutant) + GSK3 peptide + AMPPNP
3d0e - Rac-β hChk kinase domain (mutant) + inhibitor

Rac-γ hChk

2x18 – Rac-γ hChk PH domain

A-Raf

1wxm – hA-Raf RAS-binding domain - NMR

B-Raf

1uwh, 3c4c – hB-Raf kinase domain + anticancer drug
1uwj – hB-Raf kinase domain (mutant) + anticancer drug
2fb8, 3d4q, 3ii5, 3psd, 3skc, 3tv6, 4g9c, 4ksp, 4ksq, 3psb, 3ppj, 3ppk, 3prf, 3pri, 3tv4, 4dbn, 4e4x, 4mbj, 4ehe, 3q4c, 3q96, 3e26, 4h58, 4e26, 4fc0, 4pp7 – hB-Raf kinase domain + pyrazole inhibitor
4jvg, 4ehg, 4fk3, 3idp, 4g9r – hB-Raf kinase domain (mutant) + pyrazole 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, 3uc3, 3udb, 3zut, 3zuu – AtChk Srk2E kinase domain (mutant) – Arabidopsis thaliana
3ujg – AtChk Srk2E kinase domain (mutant) + protein phosphatase 2C

MAPK-interacting Chk

2hw6 – hChk 1 catalytic domain
2hw7 – hChk 1 catalytic domain + staurosporin
2ac3 – hChk 2
2ac5 – hChk 2 (mutant)

hChk Pak

1f3m – hChk Pak-1
1yhv, 1yhw, 3q4z, 3q52, 3q53 – hChk Pak-1 (mutant)
4daw – hChk Pak-1 (mutant) + Ru phthalimide
4o0r, 4o0t – hChk Pak-1 + inhibitor
4eqc – hChk Pak-1 (mutant) + inhibitor
2hy8 – hChk Pak-1 + staurosporin
2qme – hChk Pak-1 CRIB domain + RAC3
3fxz, 3fy0 – hChk Pak-1 kinase domain (mutant) + Ru complex
2j0i, 4fie – hChk Pak-4
4fig, 4fij, 4l67 – hChk Pak-4 kinase domain
2cdz – hChk Pak-4 + purine derivative
2ov2 – hChk Pak-4 CRIB domain + RAC3
2qon, 4fif, 4fih, 4fii, 4jdh, 4jdi, 4jdj, 4jdk – hChk Pak-4 kinase domain + peptide
4app, 4o0v, 4o0x, 4o0y – hChk Pak-4 kinase domain + inhibitor
2x4z, 2xh5 – hChk Pak-4 kinase domain (mutant) + inhibitor
2c30 – hChk Pak-6
2odb – hChk Pak-6 CRIB domain + CDC42
4ks8 – hChk Pak-6 kinase domain + sunitinib
4ks7 – hChk Pak-6 kinase domain (mutant) + inhibitor
2f57 – hChk Pak-7

Mycobacterium tuberculosis Chk Pkn

3ori, 3ork, 3orl, 3orm, 3oro, 3orp, 3ort - MtChk PknB kinase domain (mutant) – Mycobacterium tuberculosis
3ouv - MtChk PknB extracellular domain
1o6y – MtChk PknB catalytic domain
2kud, 2kue, 2kuf, 2kui – MtChk PknB pasta domains - NMR
3f61, 3f69 - MtChk PknB kinase domain (mutant) + inhibitor
1rwi, 1rwl - MtChk PknD extracellular domain
2h34 – MtChk PknE catalytic domain
4esq - MtChk PknH extracellular domain

hChk Nek

4apc – hChk Nek1 kinase domain (mutant)
4b9d - hChk Nek1 kinase domain (mutant) + inhibitor
2w5h – hChk Nek2 kinase domain
2jav, 2wqo, 2xk3, 2xk4, 2xk6, 2xk7, 2xk8, 2xkc, 2xkd, 2xke, 2xkf, 2xnm, 2xnn, 2xno, 2xnp, 4a4x, 4afe – hChk Nek2 + inhibitor
2w5a, 2w5b – hChk Nek2 + nucleotide
2wqm – hChk Nek7
2wqn – hChk Nek7 + ADP

TANK-binding kinase

4efo – hChk Tbk1 ubiquitin-like domain
4im0, 4im2, 4im3, 4iw0, 4iwo, 4iwp, 4ipq – hChk Tbk1 (mutant) + inhibitor
4eut, 4euu – hChk Tbk1 kinase+ubiquitin-like domains (mutant) + inhibitor
4jl9, 4jlc – mChk Tbk1 + inhibitor

Mechanistic target of rapamycin

2rse – hChk Mtor + FKBP1A - NMR
4drh, 4dri, 4drj – hChk Mtor + FKBP + rapamycin
4jsn, 4jsp, 4jsv, 4jsx, 4jt5, 4jt6 – hChk Mtor + target of rapamycin complex

Haspin

2vuw, 2wb8 – hChk Haspin kinase domain
3dle – hChk Haspin kinase domain + AMP
3e7v, 3f2n, 3fmd, 3iq7 – hChk Haspin kinase domain + inhibitor
4ouc – hChk Haspin kinase domain + histone H3 peptide

MAP/microtubule affinity-regulating kinase (Mark)

2r0i – rChk Mark1 catalytic+UBA domains (mutant)
2wzj – rChk Mark2 catalytic+UBA domains (mutant)
2hak – hChk Mark1 catalytic+UBA domains
3ose - hChk Mark1 kinase domain
3iec – hChk Mark1 catalytic+UBA domains + cytotoxicity-associated immunodominant antigen

Mitotic checkpoint Chk Bub

2lah – hChk Bub1 N terminal – NMR
2wvi – hChk Bub1β N terminal
3e7e – hChk Bub1 residues 724-1025
3si5 – hChk Bub1 residues 67-220 + CASC5 peptide
4a1g – hChk Bub1 TPR domain + CASC5 KI motif
4ggd - hChk Bub1 + cell division cycle protein
3esl – yChk Bub1 N terminal
4bl0 - yChk Bub1 + cell cycle arrest protein Bub3

Microtubule-associated Chk

2m9x – hChk 1 residues 187-287 – NMR
3ps4 - hChk 1 residues 965-1057
2kqf, 2kyl – hChk 2 PDZ domain + glycoprotein C terminal – NMR
3khf - hChk 3 PDZ domain
2w7r – hChk 4 PDZ domain

Various Chk

1u5q, 1u5r – rChk Tao2 kinase domain
2lru – rChk Wnk1 autoinhibitory domain - NMR
2cos – Chk Lats2 – mouse – NMR
1wak – hChk Sprk1
2kty, 2kul, 2lav, 2rsv – hChk Vrk1 - NMR
3op5 – hChk Vrk1 kinase domain (mutant)
2v62 – hChk Vrk2 kinase domain
3dak – hChk Osr1 kinase domain
3fpq - hChk Wnk1 kinase domain (mutant)
4aw2 – hChk Mrckα kinase domain
1how, 1zxe, 1zy4 – yChk (mutant)
1q8z, 1zyc – yChk
1ow5, 1x9x – yChk Ste11 SAM domain – NMR
2kio, 2kit – yChk Tor1 FATC domain – NMR
2yz0 – yChk Gcn2 RWD/GI domain – NMR
4otm – yChk Gcn2 C terminal domain
3gre – yChk Vps15 WD repeat domain
3osm, 3ost - yChk Kcc4 kinase domain
1uf0 – hChk Dcamkl1 DCX domain – NMR
1xte, 1xtn – mChk Sgk3 PX domain
3tpd, 3tpe – EcChk Hipa – Escherichia coli
3tpb – EcChk Hipa (mutant)
4f0g – smChk Roco4 kinase domain – slime mold

Various Chk complexes

2gcd – rChk Tao2 kinase domain + staurosporin
3hgk – Chk Pto + effector protein AVRPTOB – Currant tomato
1wbp – hChk Sprk1 + peptide
3beg – hChk Srpk1 + splicing factor SF2
3hdm, 3hdn – hChk Sgk1 (mutant) + inhibitor
2r5t – hChk Sgk3 + AMPPNP
2uv2 – hChk Ste20 + inhibitor
2v3s – hChk Osr1 + hChk Wnk4 peptide
2vwi – hChk Osr1 kinase domain + ANP
3ggf – hChk Mst4 + inhibitor
4geh, 3w8i - hChk Mst4 dimerization domain + programmed cell death protein 10
4fza, 4fzd, 4fzf – hChk Mst4 (mutant) + calcium-binding protein
4crs – hChk N2 kinase domain + ATPγS
3tku – hChk Mrckβ + fasudil
1q8y, 1q97, 1q99, 1zyd – yChk + nucleotide
1zy5 – yChk (mutant) + nucleotide
2jd5 – yChk + NPL-3P
3p86, 3ppz - AtChk Ctr1 + staurosporin
3tpt – EcChk Hipa (mutant) + ADP
3tpv – EcChk Hipa + ADP
4f0f – smChk Roco4 kinase domain + APPCP
4f1m, 4f1o – smChk Roco4 kinase domain (mutant) + APPCP
4f1t – smChk Roco4 kinase domain + inhibitor

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