2xkc: Difference between revisions

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-[[Image:2xkc.png|left|200px]]
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+==Structure of Nek2 bound to aminopyrazine compound 14==
-The line below this paragraph, containing "STRUCTURE_2xkc", creates the "Structure Box" on the page.
+<StructureSection load='2xkc' size='340' side='right'caption='[[2xkc]], [[Resolution|resolution]] 2.50&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'>[[2xkc]] 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=2XKC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XKC 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]] 2.5&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4VQ:4-[3-AMINO-6-(3,4,5-TRIMETHOXYPHENYL)PYRAZIN-2-YL]-2-METHYLBENZOIC+ACID'>4VQ</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
-{{STRUCTURE_2xkc|  PDB=2xkc  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2xkc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xkc OCA], [https://pdbe.org/2xkc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xkc RCSB], [https://www.ebi.ac.uk/pdbsum/2xkc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xkc 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 report herein the first systematic exploration of inhibitors of the mitotic kinase Nek2. Starting from HTS hit aminopyrazine 2, compounds with improved activity were identified using structure-based design. Our structural biology investigations reveal two notable observations. First, 2 and related compounds bind to an unusual, inactive conformation of the kinase which to the best of our knowledge has not been reported for other types of kinase inhibitors. Second, a phenylalanine residue at the center of the ATP pocket strongly affects the ability of the inhibitor to bind to the protein. The implications of these observations are discussed, and the work described here defines key features for potent and selective Nek2 inhibition, which will aid the identification of more advanced inhibitors of Nek2.
-===STRUCTURE OF NEK2 BOUND TO AMINOPYRAZINE COMPOUND 14===
+Aminopyrazine Inhibitors Binding to an Unusual Inactive Conformation of the Mitotic Kinase Nek2: SAR and Structural Characterization.,Whelligan DK, Solanki S, Taylor D, Thomson DW, Cheung KM, Boxall K, Mas-Droux C, Barillari C, Burns S, Grummitt CG, Collins I, van Montfort RL, Aherne GW, Bayliss R, Hoelder S J Med Chem. 2010 Oct 11. PMID:20936789<ref>PMID:20936789</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 2xkc" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_20936789}}, adds the Publication Abstract to the page
+*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 20936789 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_20936789}}
+__TOC__
+</StructureSection>
-==About this Structure==
-[[2xkc]] 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=2XKC OCA].
-==Reference==
-<ref group="xtra">PMID:020936789</ref><references group="xtra"/>
 [[Category: Homo sapiens]]
-[[Category: Non-specific serine/threonine protein kinase]]
+[[Category: Large Structures]]
-[[Category: Bayliss, R.]]
+[[Category: Bayliss R]]
-[[Category: Mas-Droux, C.]]
+[[Category: Mas-Droux C]]