Serine/threonine protein kinase

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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.

Contents 1 3D structures of serine/threonine protein kinase 1.1 Mycobacterium tuberculosis Chk Pkn 1.2 hChk Nek 1.3 TANK-binding kinase 1.4 Mechanistic target of rapamycin 1.5 Haspin 1.6 MAP/microtubule affinity-regulating kinase (Mark) 1.7 Mitotic checkpoint Chk Bub 1.8 Microtubule-associated Chk 1.9 Various Chk 1.10 Various Chk complexes

3D structures of serine/threonine protein kinase

Updated on 10-December-2014 {{#tree:id=OrganizedByTopic|openlevels=0|

• 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