1z57

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[[Image:1z57.png|left|200px]]
 
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{{STRUCTURE_1z57| PDB=1z57 | SCENE= }}
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==Crystal structure of human CLK1 in complex with 10Z-Hymenialdisine==
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<StructureSection load='1z57' size='340' side='right'caption='[[1z57]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1z57]] is a 1 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=1Z57 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Z57 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DBQ:DEBROMOHYMENIALDISINE'>DBQ</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1z57 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1z57 OCA], [https://pdbe.org/1z57 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1z57 RCSB], [https://www.ebi.ac.uk/pdbsum/1z57 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1z57 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/CLK1_HUMAN CLK1_HUMAN] Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates. Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex and may be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing. Phosphorylates: SRSF1, SRSF3 and PTPN1. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells and adenovirus E1A pre-mRNA.<ref>PMID:10480872</ref> <ref>PMID:19168442</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/z5/1z57_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1z57 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Splicing requires reversible phosphorylation of serine/arginine-rich (SR) proteins, which direct splice site selection in eukaryotic mRNA. These phosphorylation events are dependent on SR protein (SRPK) and cdc2-like kinase (CLK) families. SRPK1 phosphorylation of splicing factors is restricted by a specific docking interaction whereas CLK activity is less constrained. To understand functional differences between splicing factor targeting kinases, we determined crystal structures of CLK1 and CLK3. Intriguingly, in CLKs the SRPK1 docking site is blocked by insertion of a previously unseen helix alphaH. In addition, substrate docking grooves present in related mitogen activating protein kinases (MAPKs) are inaccessible due to a CLK specific beta7/8-hairpin insert. Thus, the unconstrained substrate interaction together with the determined active-site mediated substrate specificity allows CLKs to complete the functionally important hyperphosphorylation of splicing factors like ASF/SF2. In addition, despite high sequence conservation, we identified inhibitors with surprising isoform specificity for CLK1 over CLK3.
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===Crystal structure of human CLK1 in complex with 10Z-Hymenialdisine===
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Kinase domain insertions define distinct roles of CLK kinases in SR protein phosphorylation.,Bullock AN, Das S, Debreczeni JE, Rellos P, Fedorov O, Niesen FH, Guo K, Papagrigoriou E, Amos AL, Cho S, Turk BE, Ghosh G, Knapp S Structure. 2009 Mar 11;17(3):352-62. PMID:19278650<ref>PMID:19278650</ref>
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{{ABSTRACT_PUBMED_19278650}}
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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==About this Structure==
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<div class="pdbe-citations 1z57" style="background-color:#fffaf0;"></div>
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[[1z57]] is a 1 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=1Z57 OCA].
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==See Also==
==See Also==
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*[[Dual specificity protein kinase|Dual specificity protein kinase]]
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*[[Dual specificity protein kinase 3D structures|Dual specificity protein kinase 3D structures]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:019278650</ref><references group="xtra"/>
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__TOC__
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[[Category: Dual-specificity kinase]]
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Amos, A.]]
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[[Category: Large Structures]]
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[[Category: Arrowsmith, C.]]
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[[Category: Amos A]]
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[[Category: Ball, L.]]
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[[Category: Arrowsmith C]]
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[[Category: Bullock, A.]]
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[[Category: Ball L]]
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[[Category: Das, S.]]
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[[Category: Bullock A]]
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[[Category: Debreczeni, J.]]
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[[Category: Das S]]
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[[Category: Delft, F von.]]
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[[Category: Debreczeni J]]
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[[Category: Edwards, A.]]
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[[Category: Edwards A]]
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[[Category: Fedorov, O.]]
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[[Category: Fedorov O]]
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[[Category: Guo, K.]]
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[[Category: Guo K]]
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[[Category: Knapp, S.]]
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[[Category: Knapp S]]
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[[Category: Niesen, F H.]]
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[[Category: Niesen FH]]
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[[Category: SGC, Structural Genomics Consortium.]]
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[[Category: Sobott F]]
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[[Category: Sobott, F.]]
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[[Category: Sundstrom M]]
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[[Category: Sundstrom, M.]]
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[[Category: Von Delft F]]
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[[Category: 10z-hymendialdisine]]
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[[Category: Dual specificity]]
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[[Category: Human]]
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[[Category: Protein tyrosine kinase]]
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[[Category: Sgc]]
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[[Category: Splicing]]
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[[Category: Structural genomic]]
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[[Category: Structural genomics consortium]]
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[[Category: Transferase]]
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Current revision

Crystal structure of human CLK1 in complex with 10Z-Hymenialdisine

PDB ID 1z57

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