3kn6: Difference between revisions

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-[[Image:3kn6.png|left|200px]]
-<!--
+==Crystal structure of the C-terminal kinase domain of MSK1==
-The line below this paragraph, containing "STRUCTURE_3kn6", creates the "Structure Box" on the page.
+<StructureSection load='3kn6' size='340' side='right'caption='[[3kn6]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[3kn6]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KN6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3KN6 FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</td></tr>
--->
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3kn6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kn6 OCA], [https://pdbe.org/3kn6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3kn6 RCSB], [https://www.ebi.ac.uk/pdbsum/3kn6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3kn6 ProSAT]</span></td></tr>
-{{STRUCTURE_3kn6|  PDB=3kn6  |  SCENE=  }}
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/KS6A5_HUMAN KS6A5_HUMAN] Serine/threonine-protein kinase that is required for the mitogen or stress-induced phosphorylation of the transcription factors CREB1 and ATF1 and for the regulation of the transcription factors RELA, STAT3 and ETV1/ER81, and that contributes to gene activation by histone phosphorylation and functions in the regulation of inflammatory genes. Phosphorylates CREB1 and ATF1 in response to mitogenic or stress stimuli such as UV-C irradiation, epidermal growth factor (EGF) and anisomycin. Plays an essential role in the control of RELA transcriptional activity in response to TNF and upon glucocorticoid, associates in the cytoplasm with the glucocorticoid receptor NR3C1 and contributes to RELA inhibition and repression of inflammatory gene expression. In skeletal myoblasts is required for phosphorylation of RELA at 'Ser-276' during oxidative stress. In erythropoietin-stimulated cells, is necessary for the 'Ser-727' phosphorylation of STAT3 and regulation of its transcriptional potential. Phosphorylates ETV1/ER81 at 'Ser-191' and 'Ser-216', and thereby regulates its ability to stimulate transcription, which may be important during development and breast tumor formation. Directly represses transcription via phosphorylation of 'Ser-1' of histone H2A. Phosphorylates 'Ser-10' of histone H3 in response to mitogenics, stress stimuli and EGF, which results in the transcriptional activation of several immediate early genes, including proto-oncogenes c-fos/FOS and c-jun/JUN. May also phosphorylate 'Ser-28' of histone H3. Mediates the mitogen- and stress-induced phosphorylation of high mobility group protein 1 (HMGN1/HMG14). In lipopolysaccharide-stimulated primary macrophages, acts downstream of the Toll-like receptor TLR4 to limit the production of pro-inflammatory cytokines. Functions probably by inducing transcription of the MAP kinase phosphatase DUSP1 and the anti-inflammatory cytokine interleukin 10 (IL10), via CREB1 and ATF1 transcription factors. Plays a role in neuronal cell death by mediating the downstream effects of excitotoxic injury.<ref>PMID:11909979</ref> <ref>PMID:12569367</ref> <ref>PMID:12628924</ref> <ref>PMID:12763138</ref> <ref>PMID:12773393</ref> <ref>PMID:15010469</ref> <ref>PMID:18511904</ref> <ref>PMID:9687510</ref> <ref>PMID:9873047</ref>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kn/3kn6_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3kn6 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Mitogen- and stress-activated protein kinase 1 (MSK1) is a growth-factor-stimulated serine/threonine kinase that is involved in gene transcription regulation and proinflammatory cytokine stimulation. MSK1 is a dual kinase possessing two nonidentical protein kinase domains in one polypeptide. We present the active conformation of the crystal structures of its C-terminal kinase domain in apo form and in complex with a nonhydrolyzable ATP analogue at 2.0 A and 2.5 A resolutions, respectively. Structural analysis revealed substantial differences in the contacts formed by the C-terminal helix, which is responsible for the inactivity of other autoinhibited kinases. In the C-terminal kinase domain of MSK1, the C-terminal alphaL-helix is located in the surface groove, but forms no hydrogen bonds with the substrate-binding loop or nearby helices, and does not interfere with the protein's autophosphorylation activity. Mutational analysis confirmed that the alphaL-helix is inherently nonautoinhibitory. Overexpression of the single C-terminal kinase domain in JB6 cells resulted in tumor-promoter-induced neoplastic transformation in a manner similar to that induced by the full-length MSK1 protein. The overall results suggest that the C-terminal kinase domain of MSK1 is regulated by a novel alphaL-helix-independent mechanism, suggesting that a diverse mechanism of autoinhibition and activation might be adopted by members of a closely related protein kinase family.
-===Crystal structure of the C-terminal kinase domain of MSK1===
+The crystal structure of the active form of the C-terminal kinase domain of mitogen- and stress-activated protein kinase 1.,Malakhova M, D'Angelo I, Kim HG, Kurinov I, Bode AM, Dong Z J Mol Biol. 2010 May 28;399(1):41-52. Epub 2010 Apr 9. PMID:20382163<ref>PMID:20382163</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3kn6" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_20382163}}, adds the Publication Abstract to the page
+*[[Ribosomal protein S6 kinase 3D structures|Ribosomal protein S6 kinase 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 20382163 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_20382163}}
+__TOC__
+</StructureSection>
-==About this Structure==
-[[3kn6]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KN6 OCA].
-==Reference==
-<ref group="xtra">PMID:20382163</ref><references group="xtra"/>
 [[Category: Homo sapiens]]
-[[Category: Non-specific serine/threonine protein kinase]]
+[[Category: Large Structures]]
-[[Category: Angelo, I D.]]
+[[Category: D'Angelo I]]
-[[Category: Dong, Z.]]
+[[Category: Dong Z]]
-[[Category: Malakhova, M.]]
+[[Category: Malakhova M]]
-[[Category: Amp-pnp]]
-[[Category: Atp-binding]]
-[[Category: Kinase]]
-[[Category: Metal-binding]]
-[[Category: Msk]]
-[[Category: Msk1]]
-[[Category: Nucleotide-binding]]
-[[Category: Serine/threonine-protein kinase]]
-[[Category: Transferase]]