View source for 4yur


==Crystal Structure of Plk4 Kinase Domain Bound to Centrinone==
<StructureSection load='4yur' size='340' side='right'caption='[[4yur]], [[Resolution|resolution]] 2.65&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4yur]] 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=4YUR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YUR 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]] 2.65&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4J7:2-({2-FLUORO-4-[(2-FLUORO-3-NITROBENZYL)SULFONYL]PHENYL}SULFANYL)-5-METHOXY-N-(3-METHYL-1H-PYRAZOL-5-YL)-6-(MORPHOLIN-4-YL)PYRIMIDIN-4-AMINE'>4J7</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=4yur FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yur OCA], [https://pdbe.org/4yur PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4yur RCSB], [https://www.ebi.ac.uk/pdbsum/4yur PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4yur ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PLK4_HUMAN PLK4_HUMAN] Serine/threonine-protein kinase that plays a central role in centriole duplication. Able to trigger procentriole formation on the surface of the parental centriole cylinder, leading to the recruitment of centriole biogenesis proteins such as SASS6, CENPJ/CPAP, CCP110, CEP135 and gamma-tubulin. When overexpressed, it is able to induce centrosome amplification through the simultaneous generation of multiple procentrioles adjoining each parental centriole during S phase. Phosphorylates 'Ser-151' of FBXW5 during the G1/S transition, leading to inhibit FBXW5 ability to ubiquitinate SASS6. Its central role in centriole replication suggests a possible role in tumorigenesis, centrosome aberrations being frequently observed in tumors. Also involved in trophoblast differentiation by phosphorylating HAND1, leading to disrupt the interaction between HAND1 and MDFIC and activate HAND1. Phosphorylates CDC25C and CHEK2.<ref>PMID:16326102</ref> <ref>PMID:16244668</ref> <ref>PMID:17681131</ref> <ref>PMID:18239451</ref> <ref>PMID:19164942</ref> <ref>PMID:21725316</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Centrioles are ancient organelles that build centrosomes, the major microtubule-organizing centers of animal cells. Extra centrosomes are a common feature of cancer cells. To investigate the importance of centrosomes in the proliferation of normal and cancer cells, we developed centrinone, a reversible inhibitor of Polo-like kinase 4 (Plk4), a serine-threonine protein kinase that initiates centriole assembly. Centrinone treatment caused centrosome depletion in human and other vertebrate cells. Centrosome loss irreversibly arrested normal cells in a senescence-like G1 state by a p53-dependent mechanism that was independent of DNA damage, stress, Hippo signaling, extended mitotic duration, or segregation errors. In contrast, cancer cell lines with normal or amplified centrosome numbers could proliferate indefinitely after centrosome loss. Upon centrinone washout, each cancer cell line returned to an intrinsic centrosome number "set point." Thus, cells with cancer-associated mutations fundamentally differ from normal cells in their response to centrosome loss.

Cell biology. Reversible centriole depletion with an inhibitor of Polo-like kinase 4.,Wong YL, Anzola JV, Davis RL, Yoon M, Motamedi A, Kroll A, Seo CP, Hsia JE, Kim SK, Mitchell JW, Mitchell BJ, Desai A, Gahman TC, Shiau AK, Oegema K Science. 2015 Jun 5;348(6239):1155-60. doi: 10.1126/science.aaa5111. Epub 2015, Apr 30. PMID:25931445<ref>PMID:25931445</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4yur" 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: Motamedi A]]
[[Category: Shiau AK]]