View source for 3ztx


==Aurora kinase selective inhibitors identified using a Taxol-induced checkpoint sensitivity screen.==
<StructureSection load='3ztx' size='340' side='right'caption='[[3ztx]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3ztx]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/African_clawed_frog African clawed frog]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZTX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZTX FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZTX:2-((4-(4-HYDROXYPIPERIDIN-1-YL)PHENYL)AMINO)-5,11-DIMETHYL-5H-BENZO[E]PYRIMIDO+[5,4-B][1,4]DIAZEPIN-6(11H)-ONE'>ZTX</scene></td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2bfx|2bfx]], [[2vgo|2vgo]], [[2vrx|2vrx]], [[2vgp|2vgp]], [[2bfy|2bfy]]</div></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></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=3ztx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ztx OCA], [https://pdbe.org/3ztx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ztx RCSB], [https://www.ebi.ac.uk/pdbsum/3ztx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ztx ProSAT]</span></td></tr>
</table>
== Function ==
[[https://www.uniprot.org/uniprot/AUKBA_XENLA AUKBA_XENLA]] Serine/threonine-protein kinase component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly. Involved in the bipolar attachment of spindle microtubules to kinetochores and is a key regulator for the onset of cytokinesis during mitosis. Required for central/midzone spindle assembly and cleavage furrow formation. Phosphorylates 'Ser-10' of histone H3 during mitosis.<ref>PMID:12221116</ref> <ref>PMID:11350965</ref> <ref>PMID:17199039</ref>  [[https://www.uniprot.org/uniprot/INCEA_XENLA INCEA_XENLA]] Component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly. Probably acts through association with aurkb or aurkc. Seems to bind directly to microtubules.<ref>PMID:12221116</ref> <ref>PMID:17199039</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The members of the Aurora kinase family play critical roles in the regulation of the cell cycle and mitotic spindle assembly and have been intensively investigated as potential targets for a new class of anticancer drugs. We describe a new highly potent and selective class of Aurora kinase inhibitors discovered using a phenotypic cellular screen. Optimized inhibitors display many of the hallmarks of Aurora inhibition including endoreduplication, polyploidy, and loss of cell viability in cancer cells. Structure-activity relationships with respect to kinome-wide selectivity and guided by an Aurora B co-crystal structure resulted in the identification of key selectivity determinants and discovery of a subseries with selectivity toward Aurora A. A direct comparison of biochemical and cellular profiles with respect to published Aurora inhibitors including VX-680, AZD1152, MLN8054, and a pyrimidine-based compound from Genentech demonstrates that compounds 1 and 3 will become valuable additional pharmacological probes of Aurora-dependent functions.

Selective aurora kinase inhibitors identified using a taxol-induced checkpoint sensitivity screen.,Kwiatkowski N, Deng X, Wang J, Tan L, Villa F, Santaguida S, Huang HC, Mitchison T, Musacchio A, Gray N ACS Chem Biol. 2012 Jan 20;7(1):185-96. Epub 2011 Oct 21. PMID:21992004<ref>PMID:21992004</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3ztx" style="background-color:#fffaf0;"></div>

==See Also==
*[[Centromere protein 3D structure|Centromere protein 3D structure]]
*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: African clawed frog]]
[[Category: Large Structures]]
[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Gray, N]]
[[Category: Kwiatkowski, N]]
[[Category: Musacchio, A]]
[[Category: Villa, F]]
[[Category: Taxol-induced checkpoint inhibitor]]
[[Category: Transferase]]
[[Category: Transferase-cell cycle complex]]