2w5h

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{{Seed}}
 
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[[Image:2w5h.png|left|200px]]
 
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==Human Nek2 kinase Apo==
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The line below this paragraph, containing "STRUCTURE_2w5h", creates the "Structure Box" on the page.
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<StructureSection load='2w5h' size='340' side='right'caption='[[2w5h]], [[Resolution|resolution]] 2.33&Aring;' scene=''>
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2w5h]] 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=2W5H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2W5H 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]] 2.33&#8491;</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=2w5h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2w5h OCA], [https://pdbe.org/2w5h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2w5h RCSB], [https://www.ebi.ac.uk/pdbsum/2w5h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2w5h ProSAT]</span></td></tr>
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{{STRUCTURE_2w5h| PDB=2w5h | SCENE= }}
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/NEK2_HUMAN NEK2_HUMAN] Protein kinase which is involved in the control of centrosome separation and bipolar spindle formation in mitotic cells and chromatin condensation in meiotic cells. Regulates centrosome separation (essential for the formation of bipolar spindles and high-fidelity chromosome separation) by phosphorylating centrosomal proteins such as CROCC, CEP250 and NINL, resulting in their displacement from the centrosomes. Regulates kinetochore microtubule attachment stability in mitosis via phosphorylation of NDC80. Involved in regulation of mitotic checkpoint protein complex via phosphorylation of CDC20 and MAD2L1. Plays an active role in chromatin condensation during the first meiotic division through phosphorylation of HMGA2. Phosphorylates: PPP1CC; SGOL1; NECAB3 and NPM1. Essential for localization of MAD2L1 to kinetochore and MAPK1 and NPM1 to the centrosome. Isoform 1 phosphorylates and activates NEK11 in G1/S-arrested cells. Isoform 2, which is not present in the nucleolus, does not.<ref>PMID:11742531</ref> <ref>PMID:14978040</ref> <ref>PMID:12857871</ref> <ref>PMID:15358203</ref> <ref>PMID:15388344</ref> <ref>PMID:15161910</ref> <ref>PMID:17283141</ref> <ref>PMID:17621308</ref> <ref>PMID:17626005</ref> <ref>PMID:18086858</ref> <ref>PMID:18297113</ref> <ref>PMID:20034488</ref> <ref>PMID:21076410</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/w5/2w5h_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=2w5h 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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The Nek family of serine/threonine kinases regulates centrosome and cilia function; in addition, several of its members are potential targets for drug discovery. Nek2 is dimeric, is cell cycle regulated and functions in the separation of centrosomes at G2/M. Here, we report the crystal structures of wild-type human Nek2 kinase domain bound to ADP at 1.55-A resolution and T175A mutant in apo form as well as that bound to a non-hydrolyzable ATP analog. These show that regions of the Nek2 structure around the nucleotide-binding site can adopt several different but well-defined conformations. None of the conformations was the same as that observed for the previously reported inhibitor-bound structure, and the two nucleotides stabilized two conformations. The structures suggest mechanisms for the auto-inhibition of Nek2 that we have tested by mutagenesis. Comparison of the structures with Aurora-A and Cdk2 gives insight into the structural mechanism of Nek2 activation. The production of specific inhibitors that target individual kinases of the human genome is an urgent challenge in drug discovery, and Nek2 is especially promising as a cancer target. We not only identify potential challenges to the task of producing Nek2 inhibitors but also propose that the conformational variability provides an opportunity for the design of Nek2 selective inhibitors because one of the conformations may provide a unique target.
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===HUMAN NEK2 KINASE APO===
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Insights into the conformational variability and regulation of human Nek2 kinase.,Westwood I, Cheary DM, Baxter JE, Richards MW, van Montfort RL, Fry AM, Bayliss R J Mol Biol. 2009 Feb 20;386(2):476-85. Epub 2008 Dec 24. PMID:19124027<ref>PMID:19124027</ref>
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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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<div class="pdbe-citations 2w5h" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_19124027}}, adds the Publication Abstract to the page
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*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 19124027 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_19124027}}
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__TOC__
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</StructureSection>
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==About this Structure==
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2W5H is a 1 chain structure of 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=2W5H OCA].
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==Reference==
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<ref group="xtra">PMID:19124027</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Non-specific serine/threonine protein kinase]]
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[[Category: Large Structures]]
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[[Category: Bayliss, R.]]
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[[Category: Bayliss R]]
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[[Category: Alternative splicing]]
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[[Category: Atp-binding]]
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[[Category: Cell cycle]]
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[[Category: Cell division]]
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[[Category: Centrosome splitting]]
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[[Category: Coiled coil]]
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[[Category: Cytoplasm]]
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[[Category: Kinase]]
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[[Category: Magnesium]]
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[[Category: Meiosis]]
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[[Category: Metal-binding]]
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[[Category: Mitosis]]
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[[Category: Nucleotide-binding]]
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[[Category: Nucleus]]
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[[Category: Phosphoprotein]]
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[[Category: Polymorphism]]
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[[Category: Ser/thr protein kinase]]
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[[Category: Serine/threonine-protein kinase]]
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[[Category: Transferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Sep 3 16:27:08 2009''
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Current revision

Human Nek2 kinase Apo

PDB ID 2w5h

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