3op5: Difference between revisions

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-{{Seed}}
-[[Image:3op5.jpg|left|200px]]
-<!--
+==Human vaccinia-related kinase 1==
-The line below this paragraph, containing "STRUCTURE_3op5", creates the "Structure Box" on the page.
+<StructureSection load='3op5' size='340' side='right'caption='[[3op5]], [[Resolution|resolution]] 2.40&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'>[[3op5]] is a 4 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=3OP5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3OP5 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]] 2.4&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=REB:[4-({4-[(5-CYCLOPROPYL-1H-PYRAZOL-3-YL)AMINO]PYRIMIDIN-2-YL}AMINO)PHENYL]ACETONITRILE'>REB</scene></td></tr>
-{{STRUCTURE_3op5|  PDB=3op5  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3op5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3op5 OCA], [https://pdbe.org/3op5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3op5 RCSB], [https://www.ebi.ac.uk/pdbsum/3op5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3op5 ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/VRK1_HUMAN VRK1_HUMAN] Pontocerebellar hypoplasia type 1. The disease is caused by mutations affecting the gene represented in this entry.
+== Function ==
+[https://www.uniprot.org/uniprot/VRK1_HUMAN VRK1_HUMAN] Serine/threonine kinase involved in Golgi disassembly during the cell cycle: following phosphorylation by PLK3 during mitosis, required to induce Golgi fragmentation. Acts by mediating phosphorylation of downstream target protein. Phosphorylates 'Thr-18' of p53/TP53 and may thereby prevent the interaction between p53/TP53 and MDM2. Phosphorylates casein and histone H3. Phosphorylates BANF1: disrupts its ability to bind DNA, reduces its binding to LEM domain-containing proteins and causes its relocalization from the nucleus to the cytoplasm. Phosphorylates ATF2 which activates its transcriptional activity.<ref>PMID:10951572</ref> <ref>PMID:14645249</ref> <ref>PMID:15105425</ref> <ref>PMID:16495336</ref> <ref>PMID:18617507</ref> <ref>PMID:19103756</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/op/3op5_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=3op5 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The human genome encodes two active Vaccinia-related protein kinases (VRK), VRK1 and VRK2. These proteins have been implicated in a number of cellular processes and linked to a variety of tumors. However, understanding the cellular role of VRKs and establishing their potential use as targets for therapeutic intervention has been limited by the lack of tool compounds that can specifically modulate the activity of these kinases in cells. Here we identified BI-D1870, a dihydropteridine inhibitor of RSK kinases, as a promising starting point for the development of chemical probes targeting the active VRKs. We solved co-crystal structures of both VRK1 and VRK2 bound to BI-D1870 and of VRK1 bound to two broad-spectrum inhibitors. These structures revealed that both VRKs can adopt a P-loop folded conformation, which is stabilized by different mechanisms on each protein. Based on these structures, we suggest modifications to the dihydropteridine scaffold that can be explored to produce potent and specific inhibitors towards VRK1 and VRK2.
-===Human vaccinia-related kinase 1===
+Structural characterization of human Vaccinia-Related Kinases (VRK) bound to small-molecule inhibitors identifies different P-loop conformations.,Counago RM, Allerston CK, Savitsky P, Azevedo H, Godoi PH, Wells CI, Mascarello A, de Souza Gama FH, Massirer KB, Zuercher WJ, Guimaraes CRW, Gileadi O Sci Rep. 2017 Aug 8;7(1):7501. doi: 10.1038/s41598-017-07755-y. PMID:28790404<ref>PMID:28790404</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3op5" style="background-color:#fffaf0;"></div>
-==About this Structure==
+==See Also==
-OP5 is a 4 chains structure with sequences 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=3OP5 OCA].
+*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Non-specific serine/threonine protein kinase]]
+[[Category: Large Structures]]
-[[Category: Allerston, C K.]]
+[[Category: Allerston CK]]
-[[Category: Arrowsmith, C H.]]
+[[Category: Arrowsmith CH]]
-[[Category: Berridge, G.]]
+[[Category: Berridge G]]
-[[Category: Bountra, C.]]
+[[Category: Bountra C]]
-[[Category: Brenner, B.]]
+[[Category: Brenner B]]
-[[Category: Chalk, R.]]
+[[Category: Chalk R]]
-[[Category: Das, S.]]
+[[Category: Das S]]
-[[Category: Delft, F von.]]
+[[Category: Edwards AM]]
-[[Category: Edwards, A M.]]
+[[Category: Elkins JM]]
-[[Category: Elkins, J M.]]
+[[Category: Eswaran J]]
-[[Category: Eswaran, J.]]
+[[Category: Fedorov O]]
-[[Category: Fedorov, O.]]
+[[Category: Filippakopoulos P]]
-[[Category: Filippakopoulos, P.]]
+[[Category: Gileadi O]]
-[[Category: Gileadi, O.]]
+[[Category: Keates T]]
-[[Category: Keates, T.]]
+[[Category: King O]]
-[[Category: King, O.]]
+[[Category: Knapp S]]
-[[Category: Knapp, S.]]
+[[Category: Krojer T]]
-[[Category: Krojer, T.]]
+[[Category: Rellos P]]
-[[Category: Rellos, P.]]
+[[Category: Savitsky P]]
-[[Category: SGC, Structural Genomics Consortium.]]
+[[Category: Uttarkar S]]
-[[Category: Savitsky, P.]]
+[[Category: Weigelt J]]
-[[Category: Uttarkar, S.]]
+[[Category: Von Delft F]]
-[[Category: Weigelt, J.]]
-[[Category: Adenosine triphosphate]]
-[[Category: Amino acid sequence]]
-[[Category: Binding site]]
-[[Category: Catalytic domain]]
-[[Category: Model]]
-[[Category: Molecular]]
-[[Category: Molecular sequence data]]
-[[Category: Phosphotransferase]]
-[[Category: Protein conformation]]
-[[Category: Protein folding]]
-[[Category: Sgc]]
-[[Category: Structural genomic]]
-[[Category: Structural genomics consortium]]
-[[Category: Surface entropy reduction]]
-[[Category: Transferase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Sep 22 14:50:20 2010''