Serine/threonine protein kinase

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<StructureSection load='' size='450' side='right' scene='Journal:JBIC:2/Opening/1' caption='Crystal Structure of Glycogen Synthase Kinase 3ß bound to Anticancer Ruthenium Complex'>
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<StructureSection load='' size='350' side='right' scene='Journal:JBIC:2/Opening/1' caption='Crystal Structure of Glycogen Synthase Kinase 3ß bound to Anticancer Ruthenium Complex'>
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* '''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.<br />
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__TOC__
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== Function ==
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* '''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<ref>PMID:12781359</ref>.<br />
 +
* [[Cyclin-dependent kinases]]
* '''Chk2 (Checkpoint kinase 2)''' phosphorylates cdc25C at Ser-216. <br />
* '''Chk2 (Checkpoint kinase 2)''' phosphorylates cdc25C at Ser-216. <br />
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* '''Chk6''' called also '''Aurora A''' is critical for the formation of mitotic spindles during cellular mitosis. Chk6 is phosphorylated at residues Thr287 and Thr288.<br />
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* '''Chk6''' called also '''Aurora A''' is critical for the formation of mitotic spindles during cellular mitosis. Chk6 is phosphorylated at residues Thr287 and Thr288<ref>PMID:15501446</ref>.<br />
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* '''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).
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* '''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)<ref>PMID:15640844</ref>.
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* '''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.
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* '''Chk11''' see [[STK11]].
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* '''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]].
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* '''Chk Pak''' see [[Student Project 1 for UMass Chemistry 423 Spring 2015]]<ref>PMID:19165420</ref>.
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* '''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]].
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* '''[[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<ref>PMID:17530463</ref>.
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For details on Snf1-related kinase see <br />
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* '''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<ref>PMID:12460918</ref>.
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*[[ABA-regulated SNRK2 Protein Kinase]]<br />
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See more in [[B-RAF with PLX4032]]; [[Mitogen-activated protein kinase cascade]].
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*[[ABA Signaling Pathway]].
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 +
* '''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<ref>PMID:23737487</ref>. For details on '''c-Raf''' see [[Molecular Playground/C-Raf]] and [[Mitogen-activated protein kinase cascade]]..
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'''Structure of Anticancer Ruthenium Half-Sandwich Complex Bound to Glycogen Synthase Kinase 3ß <ref>DOI 10.1007/s00775-010-0699-x</ref>'''
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* '''mTOR''' (mammalian target of [[Rapamycin]]) integrates the input from insulin, growth factors and amino acids. [[Rapamycin]] inhibits mTOR by association with FKBP12<ref>PMID:22500797</ref>. See also [[PI3K/AKT/mTOR signaling pathway]].
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&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;A crystal structure of an <scene name='Journal:JBIC:2/Half_sandwich_complex_no_bonds/1'>organometallic half-sandwich ruthenium complex </scene>bound to the protein kinase glycogen synthase kinase 3ß (GSK-3ß) has been determined and reveals that the inhibitor binds to the <scene name='Journal:JBIC:2/Atp_binding_site2/2'>ATP binding site</scene> via an induced fit mechanism utlizing several <scene name='Journal:JBIC:2/Half_sandwich_complex/3'>hydrogen bonds</scene> and <scene name='Journal:JBIC:2/Half_sandwich_hydrophobic_stic/1'>hydrophobic interactions</scene>. 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 <scene name='Journal:JBIC:2/Half_sandwich_hydrophobic/5'>sandwiched between the faces of the N- and C-terminal lobes</scene> and to interact tightly with <scene name='Journal:JBIC:2/Glycine_rich_loop2/4'>the flexible glycine-rich loop</scene>. 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.
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</StructureSection>
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==3D structures of serine/threonine protein kinase==
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* '''Gcn2''' (Generl Control Nonderepressible 2) senses amino acid deficiency by binding to uncharged tRNA<ref>PMID:26982722</ref>.
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Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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* '''PRK1''' or serine/threonine protein kinase N1 belongs th protein kinase C family. PRK1 may mediate the Rho-independent signaling pathway. For more details see [[Student Project 1 for UMass Chemistry 423 Spring 2015]].
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{{#tree:id=OrganizedByTopic|openlevels=0|
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*'''Chk1'''
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* '''Pim''' see [[Proto-oncogene serine/threonine-protein kinase]]
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**[[1ia8]] – hChk1 – human<br />
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*[[Leucine-rich repeat serine/threonine-protein kinase 2]] (LRRK2)
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**[[1zlt]] – hChk1 + hymenaldisine<br />
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**[[1nvq]], [[1nvr]] – hChk1 kinase domain+ peptide + saurosporine – human
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**[[1nvs]], [[1zys]] - hChk1 kinase domain + peptide + inhibitor
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*Protein kinase B (PKB), also known as '''AKT''', is the collective name of a set of three serine/threonine-specific protein kinases that play key roles in multiple cellular processes such as glucose metabolism, apoptosis, cell proliferation, transcription, and cell migration. For example of AKT1 see [[3mv5]]. '''Rac-α''' or '''AKT1''' acts in cell growth and survival. '''Rac-β''' or '''AKT2''' acts in metabolism. '''Rac-γ''' or '''AKT3''' acts in the nervous system.
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**[[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<br />
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For details on '''Snf1-related kinase''' see <br />
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**[[2jqi]] – yChk1 – yeast<br />
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*[[ABA-regulated SNRK2 Protein Kinase]]<br />
 +
*[[ABA Signaling Pathway]].
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*'''Chk2 (Checkpoint kinase)'''
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*See also [[Receptor protein serine/threonine kinases]]
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**[[1gxc]] – hChk2 phosphothreonine-binding domain + phosphopeptide
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==Structure of Anticancer Ruthenium Half-Sandwich Complex Bound to Glycogen Synthase Kinase 3ß <ref>DOI 10.1007/s00775-010-0699-x</ref>==
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&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;A crystal structure of an <scene name='Journal:JBIC:2/Half_sandwich_complex_no_bonds/1'>organometallic half-sandwich ruthenium complex </scene>bound to the protein kinase glycogen synthase kinase 3ß (GSK-3ß) has been determined and reveals that the inhibitor binds to the <scene name='Journal:JBIC:2/Atp_binding_site2/2'>ATP binding site</scene> via an induced fit mechanism utlizing several <scene name='Journal:JBIC:2/Half_sandwich_complex/3'>hydrogen bonds</scene> and <scene name='Journal:JBIC:2/Half_sandwich_hydrophobic_stic/1'>hydrophobic interactions</scene>. 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 <scene name='Journal:JBIC:2/Half_sandwich_hydrophobic/5'>sandwiched between the faces of the N- and C-terminal lobes</scene> and to interact tightly with <scene name='Journal:JBIC:2/Glycine_rich_loop2/4'>the flexible glycine-rich loop</scene>. 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.
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**[[2cn5]] – hChk2 kinase domain + ADP
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**[[2cn8]] – hChk2 kinase domain + inhibitor
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==3D structures of serine/threonine protein kinase==
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[[Serine/threonine protein kinase 3D structures]]
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**[[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
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**[[3i6u]], [[3i6w]] – hChk2 residues 84-502 (mutant)
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*'''Chk3 (Mst2)'''
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**[[4hkd]], [[4l0n]] – hChk3 SARAH domain<br />
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**[[4lg4]] – hChk3 kinase domain<br />
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**[[4lgd]] – hChk3 kinase domain + RASSF5 SARAH domain<br />
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*'''Chk4 (Mst1)'''
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**[[2jo8]] – hChk4 C terminal domain - NMR<br />
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**[[3com]] – hChk4 kinase domain<br />
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**[[4nr2]] – hChk4 SARAH domain<br />
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*'''Chk5 (Aurora kinase b)'''
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**[[4af3]] – hChk5 + inhibitor <br />
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*'''Chk6'''
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+
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**[[1muo]], [[1mq4]] – hChk6 kinase domain<br />
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**[[1ol6]] – hChk6 kinase domain (mutant) + ATP<br />
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**[[2wqe]] – hChk6 kinase domain (mutant) + ADP<br />
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**[[2c6d]] – hChk6 kinase domain (mutant) + ADPNP<br />
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**[[2dwb]] – hChk6 kinase domain + AMPPNP<br />
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**[[3daj]], [[3d14]], [[3dj5]], [[3dj6]], [[3dj7]], [[3d15]], [[3d2i]], [[3d2k]] – Chk6 kinase domain (mutant) + inhibitor - mouse<br />
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**[[2j4z]], [[2j50]], [[2np8]], [[3efw]], [[2x81]], [[2x6d]], [[2x6e]], [[3myg]], [[3vap]], [[4b0g]] – hChk6 kinase domain + inhibitor<br />
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**[[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<br />
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*Chk6 with phosphorylated Thr 287, Thr288
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**[[1ol5]], [[1ol7]] – hChk6 kinase domain + PThr + ADP<br />
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**[[2w1c]], [[2w1d]], [[2w1e]], [[2w1f]], [[2w1g]] – hChk6 kinase domain + PThr + inhibitor<br />
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**[[2wtv]] – hChk6 kinase domain (mutant) + PThr + inhibitor<br />
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**[[3e5a]], [[3ha6]] – hChk6 kinase domain + PThr + inhibitor + targeting protein for XKLP2<br />
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*'''Chk10'''
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**[[2j7t]], [[4aot]], [[4equ]] – hChk10 kinase domain + inhibitor<br />
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*'''Chk11'''
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**[[2wtk]] – hChk11 (mutant) + calcium-binding protein<br />
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*'''Chk12 (Aurora kinase b-a)'''
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**[[2vgo]], [[2vgp]], [[2vrx]], [[3ztx]], [[4c2v]] – fChk12 + inner centromere protein A peptide + inhibitor - frog<br />
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**[[4c2w]] – fChk12 + inner centromere protein A peptide + AMPPNP<br />
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**[[4b8l]], [[4b8m]] – fChk12 (mutant) + inner centromere protein A peptide + inhibitor <br />
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*'''Chk13 (Polo-like kinase Plk)'''
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*Plk1 Polo-box domain (Pdb)''
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**[[1q4o]], [[2ogq]], [[3hih]], [[3p2w]], [[4h5x]] – Plk1 Pbd<br />
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*Plk1 Pbd complex with polypeptide
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**[[1umw]], [[2ojx]], [[3bzi]], [[3c5l]], [[3rq7]], [[4dfw]] – Plk1 Pbd + peptide<br />
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**[[3hik]], [[3fvh]], [[3p2z]], [[3p34]], [[3p35]], [[3p36]], [[3p37]], [[3q1i]], [[4e67]], [[4e9c]], [[4e9d]], [[4hab]], [[4hy2]] – Plk1 Pbd + phosphopeptide<br />
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**[[1q4k]] – Plk1 Pbd (mutant) + phosphopeptide<br />
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**[[2v5q]] – Plk1 Pbd + design ankyrin repeat protein<br />
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**[[4lkl]] – hChk Plk1 + PL-55 <br />
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**[[4lkm]] – hChk Plk1 + PL-74 <br />
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**[[4mlu]] – hChk Plk1 + peptide <br />
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*Plk1 Pbd complex with small molecule inhibitor
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**[[4h71]], [[4hco]] – Plk1 Pbd + inhibitor<br />
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**[[2rku]] – Plk1 Pbd (mutant) + inhibitor<br />
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**[[3db6]], [[3db8]], [[3dbc]], [[3dbd]], [[3dbe]], [[3dbf]] – zfPlk1 Pbd (mutant) + inhibitor – zebra fish<br />
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*Plk1 catalytic domain
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**[[2owb]] – Plk1 catalytic domain <br />
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**[[2ou7]] – Plk1 catalytic domain + AMPPNP<br />
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**[[3d5w]] – zfPlk1 catalytic domain + ADP<br />
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**[[3kb7]], [[2yac]], [[3thb]], [[4a4l]], [[4a4o]] – Plk1 catalytic domain + inhibitor<br />
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**[[3fc2]] – Plk1catalytic domain (mutant) + inhibitor<br />
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**[[4j52]], [[4j53]] – hChk Plk1 (mutant) + inhibitor <br />
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**[[3d5x]] – zfPlk1 catalytic domain (mutant) + wortmannin<br />
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*'''Plk2'''
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**[[4i5m]], [[4i5p]], [[4i6f]], [[4i6h]] – hChk Plk2 (mutant) + inhibitor <br />
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*'''Plk3'''
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**[[4b6l]], [[4i6b]] – hChk Plk3 kinase domain + inhibitor<br />
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*'''Chk15 (Aurora kinase a)'''
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**[[4bn1]] – hChk15 (mutant) <br />
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**[[4byi]], [[4byj]], [[4jai]], [[4jaj]], [[3w10]], [[3w16]], [[3w18]], [[3w2c]] – hChk15 kinase domain + inhibitor <br />
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**[[4jbo]], [[4jbp]], [[4jbq]] – hChk15 kinase domain (mutant) + inhibitor <br />
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+
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*'''Chk16'''
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+
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**[[2buj]] – hChk13 (mutant) + staurosporin <br />
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+
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*'''Chk17'''
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**[[3lm0]] – hChk17B <br />
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**[[3lm5]] – hChk17B + quercetin<br />
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+
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*'''Chk24'''
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+
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**[[3a7f]], [[3a7g]], [[3a7h]], [[3a7i]], [[3a7j]], [[3ckw]] – hChk24 kinase domain <br />
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**[[3ckx]] – hChk24 kinase domain + staurosporin <br />
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**[[3zhp]] – hChk24 kinase domain + calcium-binding protein <br />
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+
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*'''Chk25'''
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+
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**[[2xik]] – hChk25<br />
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**[[3w8h]] – hChk25 + programmed cell death protein 10<br />
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+
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*'''Chk32'''
+
-
 
+
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**[[4fr4]] – hChk32A<br />
+
-
 
+
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*'''Rac-α hChk'''
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+
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**[[1h10]], [[1unq]], [[2uvm]] – hRac-α hChk pleckstrin homology domain + inositol tetrakisphosphate<br />
+
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**[[1unp]], [[1unr]] – hRac-α hChk pleckstrin homology domain <br />
+
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**[[2uzr]], [[2uzs]] – hRac-α hChk pleckstrin homology domain (mutant) <br />
+
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**[[3o96]], [[4ejn]] - hRac-α hChk + inhibitor<br />
+
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**[[4gv1]] - hRac-α hChk kinase domain + inhibitor<br />
+
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**[[4ekl]] - hRac-α hChk (mutant) + inhibitor<br />
+
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**[[4ekk]] - hRac-α hChk (mutant) + glycogen synthase kinase-3 peptide + AMPPNP<br />
+
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**[[3ow4]], [[3qkk]], [[3qkl]] - hRac-α hChk kinase domain (mutant) + GSK3 peptide + inhibitor<br />
+
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**[[3qkm]] - hRac-α hChk kinase domain (mutant) + inhibitor<br />
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-
 
+
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*'''Rac-β hChk'''
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**[[1gzk]], [[1gzn]], [[1gzo]], [[1mrv]], [[1mry]] – Rac-β hChk kinase domain<br />
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**[[1p6s]] - Rac-β hChk pleckstrin homology domain - NMR<br />
+
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**[[1o6k]] - Rac-β hChk kinase domain + GSK3 peptide + AMPPNP<br />
+
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**[[2jdo]], [[2jdr]], [[2uw9]], [[2x39]], [[3cqu]], [[3cqw]] - Rac-β hChk kinase domain + GSK3 peptide + inhibitor<br />
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**[[3e87]], [[3e88]], [[3e8d]] - Rac-β hChk kinase domain (mutant) + GSK3 peptide + inhibitor<br /
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**[[1o6l]] - Rac-β hChk kinase domain (mutant) + GSK3 peptide + AMPPNP<br />
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**[[3d0e]] - Rac-β hChk kinase domain (mutant) + inhibitor<br />
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+
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*'''Rac-γ hChk'''
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**[[2x18]] – Rac-γ hChk PH domain<br />
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*'''A-Raf'''
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**[[1wxm]] – hA-Raf RAS-binding domain - NMR<br />
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*'''B-Raf'''
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**[[1uwh]], [[3c4c]] – hB-Raf kinase domain + anticancer drug<br />
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**[[1uwj]] – hB-Raf kinase domain (mutant) + anticancer drug<br />
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**[[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<br />
+
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**[[4jvg]], [[4ehg]], [[4fk3]], [[3idp]], [[4g9r]] – hB-Raf kinase domain (mutant) + pyrazole inhibitor<br />
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**[[2l05]] – hB-Raf RAS-binding domain - NMR<br />
+
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**[[3ny5]] – hB-Raf RAS-binding domain <br />
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+
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*'''c-Raf'''
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**[[1rfa]] – hc-Raf RAS-binding domain - NMR<br />
+
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**[[1rrb]] – c-Raf RAS-binding domain – NMR - rat<br />
+
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**[[1faq]], [[1far]] – hc-Raf cysteine-rich domain - NMR<br />
+
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**[[3omv]] – hc-Raf kinase domain <br />
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*c-Raf complex with protein
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**[[1c1y]] – hc-Raf RAS-binding domain + RAP1A <br />
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**[[3kuc]] – hc-Raf RAS-binding domain (mutant) + RAP1A <br />
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**[[1gua]] – hc-Raf RAS-binding domain + RAP1A + GPPNHP<br />
+
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**[[4g0n]], [[4g3x]] – hc-Raf RAS-binding domain + GTPase Hras <br />
+
-
**[[3kud]] – hc-Raf RAS-binding domain (mutant) + GTPase Hras <br />
+
-
 
+
-
*'''Snf1-related Chk'''
+
-
 
+
-
**[[3uc4]], [[3uc3]], [[3udb]], [[3zut]], [[3zuu]] – AtChk Srk2E kinase domain (mutant) – ''Arabidopsis thaliana''<br />
+
-
**[[3ujg]] – AtChk Srk2E kinase domain (mutant) + protein phosphatase 2C<br />
+
-
 
+
-
*'''MAPK-interacting Chk'''
+
-
 
+
-
**[[2hw6]] – hChk 1 catalytic domain<br />
+
-
**[[2hw7]] – hChk 1 catalytic domain + staurosporin<br />
+
-
**[[2ac3]] – hChk 2<br />
+
-
**[[2ac5]] – hChk 2 (mutant)<br />
+
-
 
+
-
*'''hChk Pak'''
+
-
 
+
-
**[[1f3m]] – hChk Pak-1<br />
+
-
**[[1yhv]], [[1yhw]], [[3q4z]], [[3q52]], [[3q53]] – hChk Pak-1 (mutant)<br />
+
-
**[[4daw]] – hChk Pak-1 (mutant) + Ru phthalimide<br />
+
-
**[[4o0r]], [[4o0t]] – hChk Pak-1 + inhibitor<br />
+
-
**[[4eqc]] – hChk Pak-1 (mutant) + inhibitor<br />
+
-
**[[2hy8]] – hChk Pak-1 + staurosporin<br />
+
-
**[[2qme]] – hChk Pak-1 CRIB domain + RAC3<br />
+
-
**[[3fxz]], [[3fy0]] – hChk Pak-1 kinase domain (mutant) + Ru complex<br />
+
-
**[[2j0i]], [[4fie]] – hChk Pak-4<br />
+
-
**[[4fig]], [[4fij]], [[4l67]] – hChk Pak-4 kinase domain<br />
+
-
**[[2cdz]] – hChk Pak-4 + purine derivative<br />
+
-
**[[2ov2]] – hChk Pak-4 CRIB domain + RAC3<br />
+
-
**[[2qon]], [[4fif]], [[4fih]], [[4fii]], [[4jdh]], [[4jdi]], [[4jdj]], [[4jdk]] – hChk Pak-4 kinase domain + peptide<br />
+
-
**[[4app]], [[4o0v]], [[4o0x]], [[4o0y]] – hChk Pak-4 kinase domain + inhibitor<br />
+
-
**[[2x4z]], [[2xh5]] – hChk Pak-4 kinase domain (mutant) + inhibitor<br />
+
-
**[[2c30]] – hChk Pak-6<br />
+
-
**[[2odb]] – hChk Pak-6 CRIB domain + CDC42<br />
+
-
**[[4ks8]] – hChk Pak-6 kinase domain + sunitinib<br />
+
-
**[[4ks7]] – hChk Pak-6 kinase domain (mutant) + inhibitor<br />
+
-
**[[2f57]] – hChk Pak-7<br />
+
-
 
+
-
===''Mycobacterium tuberculosis'' Chk Pkn===
+
-
 
+
-
[[3ori]], [[3ork]], [[3orl]], [[3orm]], [[3oro]], [[3orp]], [[3ort]] - MtChk PknB kinase domain (mutant) – ''Mycobacterium tuberculosis''<br />
+
-
[[3ouv]] - MtChk PknB extracellular domain<br />
+
-
[[1o6y]] – MtChk PknB catalytic domain<br />
+
-
[[2kud]], [[2kue]], [[2kuf]], [[2kui]] – MtChk PknB pasta domains - NMR<br />
+
-
[[3f61]], [[3f69]] - MtChk PknB kinase domain (mutant) + inhibitor<br />
+
-
[[1rwi]], [[1rwl]] - MtChk PknD extracellular domain<br />
+
-
[[2h34]] – MtChk PknE catalytic domain<br />
+
-
[[4esq]] - MtChk PknH extracellular domain<br />
+
-
 
+
-
===hChk Nek===
+
-
 
+
-
[[4apc]] – hChk Nek1 kinase domain (mutant)<br />
+
-
[[4b9d]] - hChk Nek1 kinase domain (mutant) + inhibitor<br />
+
-
[[2w5h]] – hChk Nek2 kinase domain<br />
+
-
[[2jav]], [[2wqo]], [[2xk3]], [[2xk4]], [[2xk6]], [[2xk7]], [[2xk8]], [[2xkc]], [[2xkd]], [[2xke]], [[2xkf]], [[2xnm]], [[2xnn]], [[2xno]], [[2xnp]], [[4a4x]], [[4afe]] – hChk Nek2 + inhibitor<br />
+
-
[[2w5a]], [[2w5b]] – hChk Nek2 + nucleotide<br />
+
-
[[2wqm]] – hChk Nek7<br />
+
-
[[2wqn]] – hChk Nek7 + ADP<br />
+
-
 
+
-
===TANK-binding kinase===
+
-
 
+
-
[[4efo]] – hChk Tbk1 ubiquitin-like domain <br />
+
-
[[4im0]], [[4im2]], [[4im3]], [[4iw0]], [[4iwo]], [[4iwp]], [[4ipq]] – hChk Tbk1 (mutant) + inhibitor <br />
+
-
[[4eut]], [[4euu]] – hChk Tbk1 kinase+ubiquitin-like domains (mutant) + inhibitor <br />
+
-
[[4jl9]], [[4jlc]] – mChk Tbk1 + inhibitor <br />
+
-
 
+
-
===Mechanistic target of rapamycin===
+
-
 
+
-
[[2rse]] – hChk Mtor + FKBP1A - NMR <br />
+
-
[[4drh]], [[4dri]], [[4drj]] – hChk Mtor + FKBP + rapamycin <br />
+
-
[[4jsn]], [[4jsp]], [[4jsv]], [[4jsx]], [[4jt5]], [[4jt6]] – hChk Mtor + target of rapamycin complex<br />
+
-
 
+
-
===Haspin===
+
-
 
+
-
[[2vuw]], [[2wb8]] – hChk Haspin kinase domain <br />
+
-
[[3dle]] – hChk Haspin kinase domain + AMP<br />
+
-
[[3e7v]], [[3f2n]], [[3fmd]], [[3iq7]] – hChk Haspin kinase domain + inhibitor<br />
+
-
[[4ouc]] – hChk Haspin kinase domain + histone H3 peptide<br />
+
-
 
+
-
===MAP/microtubule affinity-regulating kinase (Mark)===
+
-
 
+
-
[[2r0i]] – rChk Mark1 catalytic+UBA domains (mutant)<br />
+
-
[[2wzj]] – rChk Mark2 catalytic+UBA domains (mutant)<br />
+
-
[[2hak]] – hChk Mark1 catalytic+UBA domains <br />
+
-
[[3ose]] - hChk Mark1 kinase domain <br />
+
-
[[3iec]] – hChk Mark1 catalytic+UBA domains + cytotoxicity-associated immunodominant antigen<br />
+
-
 
+
-
===Mitotic checkpoint Chk Bub===
+
-
 
+
-
[[2lah]] – hChk Bub1 N terminal – NMR<br />
+
-
[[2wvi]] – hChk Bub1β N terminal <br />
+
-
[[3e7e]] – hChk Bub1 residues 724-1025<br />
+
-
[[3si5]] – hChk Bub1 residues 67-220 + CASC5 peptide<br />
+
-
[[4a1g]] – hChk Bub1 TPR domain + CASC5 KI motif<br />
+
-
[[4ggd]] - hChk Bub1 + cell division cycle protein<br />
+
-
[[3esl]] – yChk Bub1 N terminal <br />
+
-
[[4bl0]] - yChk Bub1 + cell cycle arrest protein Bub3 <br />
+
-
 
+
-
===Microtubule-associated Chk===
+
-
 
+
-
[[2m9x]] – hChk 1 residues 187-287 – NMR<br />
+
-
[[3ps4]] - hChk 1 residues 965-1057<br />
+
-
[[2kqf]], [[2kyl]] – hChk 2 PDZ domain + glycoprotein C terminal – NMR<br />
+
-
[[3khf]] - hChk 3 PDZ domain <br />
+
-
[[2w7r]] – hChk 4 PDZ domain <br />
+
-
 
+
-
===Various Chk===
+
-
 
+
-
[[1u5q]], [[1u5r]] – rChk Tao2 kinase domain <br />
+
-
[[2lru]] – rChk Wnk1 autoinhibitory domain - NMR<br />
+
-
[[2cos]] – Chk Lats2 – mouse – NMR<br />
+
-
[[1wak]] – hChk Sprk1 <br />
+
-
[[2kty]], [[2kul]], [[2lav]], [[2rsv]] – hChk Vrk1 - NMR <br />
+
-
[[3op5]] – hChk Vrk1 kinase domain (mutant)<br />
+
-
[[2v62]] – hChk Vrk2 kinase domain <br />
+
-
[[3dak]] – hChk Osr1 kinase domain <br />
+
-
[[3fpq]] - hChk Wnk1 kinase domain (mutant)<br />
+
-
[[4aw2]] – hChk Mrckα kinase domain<br />
+
-
[[1how]], [[1zxe]], [[1zy4]] – yChk (mutant)<br />
+
-
[[1q8z]], [[1zyc]] – yChk <br />
+
-
[[1ow5]], [[1x9x]] – yChk Ste11 SAM domain – NMR<br />
+
-
[[2kio]], [[2kit]] – yChk Tor1 FATC domain – NMR<br />
+
-
[[2yz0]] – yChk Gcn2 RWD/GI domain – NMR<br />
+
-
[[4otm]] – yChk Gcn2 C terminal domain <br />
+
-
[[3gre]] – yChk Vps15 WD repeat domain<br />
+
-
[[3osm]], [[3ost]] - yChk Kcc4 kinase domain <br />
+
-
[[1uf0]] – hChk Dcamkl1 DCX domain – NMR<br />
+
-
[[1xte]], [[1xtn]] – mChk Sgk3 PX domain <br />
+
-
[[3tpd]], [[3tpe]] – EcChk Hipa – ''Escherichia coli''<br />
+
-
[[3tpb]] – EcChk Hipa (mutant) <br />
+
-
[[4f0g]] – smChk Roco4 kinase domain – slime mold<br />
+
-
 
+
-
===Various Chk complexes===
+
-
 
+
-
[[2gcd]] – rChk Tao2 kinase domain + staurosporin<br />
+
-
[[3hgk ]]– Chk Pto + effector protein AVRPTOB – Currant tomato<br />
+
-
[[1wbp]] – hChk Sprk1 + peptide<br />
+
-
[[3beg]] – hChk Srpk1 + splicing factor SF2<br />
+
-
[[3hdm]], [[3hdn]] – hChk Sgk1 (mutant) + inhibitor <br />
+
-
[[2r5t]] – hChk Sgk3 + AMPPNP <br />
+
-
[[2uv2]] – hChk Ste20 + inhibitor <br />
+
-
[[2v3s]] – hChk Osr1 + hChk Wnk4 peptide <br />
+
-
[[2vwi]] – hChk Osr1 kinase domain + ANP <br />
+
-
[[3ggf]] – hChk Mst4 + inhibitor <br />
+
-
[[4geh]], [[3w8i]] - hChk Mst4 dimerization domain + programmed cell death protein 10<br />
+
-
[[4fza]], [[4fzd]], [[4fzf]] – hChk Mst4 (mutant) + calcium-binding protein <br />
+
-
[[4crs]] – hChk N2 kinase domain + ATPγS<br />
+
-
[[3tku]] – hChk Mrckβ + fasudil<br />
+
-
[[1q8y]], [[1q97]], [[1q99]], [[1zyd]] – yChk + nucleotide<br />
+
-
[[1zy5]] – yChk (mutant) + nucleotide<br />
+
-
[[2jd5]] – yChk + NPL-3P<br />
+
-
[[3p86]], [[3ppz]] - AtChk Ctr1 + staurosporin<br />
+
-
[[3tpt]] – EcChk Hipa (mutant) + ADP<br />
+
-
[[3tpv]] – EcChk Hipa + ADP<br />
+
-
[[4f0f]] – smChk Roco4 kinase domain + APPCP <br />
+
-
[[4f1m]], [[4f1o]] – smChk Roco4 kinase domain (mutant) + APPCP <br />
+
-
[[4f1t]] – smChk Roco4 kinase domain + inhibitor <br />
+
-
+
 +
</StructureSection>
-
'''References'''
+
===References===
<references/>
<references/>
[[Category:Topic Page]]
[[Category:Topic Page]]

Current revision

Crystal Structure of Glycogen Synthase Kinase 3ß bound to Anticancer Ruthenium Complex

Drag the structure with the mouse to rotate

References

  1. ↑ Bartek J, Lukas J. Chk1 and Chk2 kinases in checkpoint control and cancer. Cancer Cell. 2003 May;3(5):421-9. PMID:12781359
  2. ↑ Ducat D, Zheng Y. Aurora kinases in spindle assembly and chromosome segregation. Exp Cell Res. 2004 Nov 15;301(1):60-7. PMID:15501446 doi:http://dx.doi.org/10.1016/j.yexcr.2004.08.016
  3. ↑ Takai N, Hamanaka R, Yoshimatsu J, Miyakawa I. Polo-like kinases (Plks) and cancer. Oncogene. 2005 Jan 10;24(2):287-91. PMID:15640844 doi:http://dx.doi.org/10.1038/sj.onc.1208272
  4. ↑ Dummler B, Ohshiro K, Kumar R, Field J. Pak protein kinases and their role in cancer. Cancer Metastasis Rev. 2009 Jun;28(1-2):51-63. doi: 10.1007/s10555-008-9168-1. PMID:19165420 doi:http://dx.doi.org/10.1007/s10555-008-9168-1
  5. ↑ Forde JE, Dale TC. Glycogen synthase kinase 3: a key regulator of cellular fate. Cell Mol Life Sci. 2007 Aug;64(15):1930-44. PMID:17530463 doi:http://dx.doi.org/10.1007/s00018-007-7045-7
  6. ↑ Brose MS, Volpe P, Feldman M, Kumar M, Rishi I, Gerrero R, Einhorn E, Herlyn M, Minna J, Nicholson A, Roth JA, Albelda SM, Davies H, Cox C, Brignell G, Stephens P, Futreal PA, Wooster R, Stratton MR, Weber BL. BRAF and RAS mutations in human lung cancer and melanoma. Cancer Res. 2002 Dec 1;62(23):6997-7000. PMID:12460918
  7. ↑ Antony R, Emery CM, Sawyer AM, Garraway LA. C-RAF mutations confer resistance to RAF inhibitors. Cancer Res. 2013 Aug 1;73(15):4840-51. doi: 10.1158/0008-5472.CAN-12-4089. Epub, 2013 Jun 4. PMID:23737487 doi:http://dx.doi.org/10.1158/0008-5472.CAN-12-4089
  8. ↑ Laplante M, Sabatini DM. mTOR signaling in growth control and disease. Cell. 2012 Apr 13;149(2):274-93. doi: 10.1016/j.cell.2012.03.017. PMID:22500797 doi:http://dx.doi.org/10.1016/j.cell.2012.03.017
  9. ↑ Ravindran R, Loebbermann J, Nakaya HI, Khan N, Ma H, Gama L, Machiah DK, Lawson B, Hakimpour P, Wang YC, Li S, Sharma P, Kaufman RJ, Martinez J, Pulendran B. The amino acid sensor GCN2 controls gut inflammation by inhibiting inflammasome activation. Nature. 2016 Mar 24;531(7595):523-7. doi: 10.1038/nature17186. Epub 2016 Mar 16. PMID:26982722 doi:http://dx.doi.org/10.1038/nature17186
  10. ↑ 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

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