View source for 2xnn


==Structure of Nek2 bound to CCT242430==
<StructureSection load='2xnn' size='340' side='right'caption='[[2xnn]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2xnn]] 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=2XNN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XNN FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=430:5-(1H-BENZIMIDAZOL-1-YL)-3-{(1R)-1-[2-(TRIFLUOROMETHYL)PHENYL]ETHOXY}THIOPHENE-2-CARBOXAMIDE'>430</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></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=2xnn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xnn OCA], [https://pdbe.org/2xnn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xnn RCSB], [https://www.ebi.ac.uk/pdbsum/2xnn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xnn ProSAT]</span></td></tr>
</table>
== Function ==
[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> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
We describe herein the structure-activity relationship (SAR) and cocrystal structures of a series of Nek2 inhibitors derived from the published polo-like kinase 1 (Plk1) inhibitor (R)-1. Our studies reveal a nonlinear SAR for Nek2 and our cocrystal structures show that compounds in this series bind to a DFG-out conformation of Nek2 without extending into the enlarged back pocket commonly found in this conformation. These observations were further investigated, and structure-based design led to Nek2 inhibitors derived from (R)-1 with more than a hundred-fold selectivity against Plk1.

Benzimidazole Inhibitors Induce a DFG-Out Conformation of Never in Mitosis Gene A-Related Kinase 2 (Nek2) without Binding to the Back Pocket and Reveal a Nonlinear Structure-Activity Relationship.,Solanki S, Innocenti P, Mas-Droux C, Boxall K, Barillari C, van Montfort RL, Aherne GW, Bayliss R, Hoelder S J Med Chem. 2011 Mar 24;54(6):1626-39. Epub 2011 Mar 2. PMID:21366329<ref>PMID:21366329</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2xnn" style="background-color:#fffaf0;"></div>

==See Also==
*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Bayliss R]]
[[Category: Mas-Droux C]]