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{{STRUCTURE_4jaj|  PDB=4jaj  |  SCENE=  }}
==Crystal Structure of Aurora Kinase A in complex with BENZO[C][1,8]NAPHTHYRIDIN-6(5H)-ONE==
===Crystal Structure of Aurora Kinase A in complex with BENZO[C][1,8]NAPHTHYRIDIN-6(5H)-ONE===
<StructureSection load='4jaj' size='340' side='right' caption='[[4jaj]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
{{ABSTRACT_PUBMED_23570792}}
== Structural highlights ==
<table><tr><td colspan='2'>[[4jaj]] 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=4JAJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4JAJ FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=XU1:BENZO[C][1,8]NAPHTHYRIDIN-6(5H)-ONE'>XU1</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4jai|4jai]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AURKA, AIK, AIRK1, ARK1, AURA, AYK1, BTAK, IAK1, STK15, STK6 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4jaj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jaj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4jaj RCSB], [http://www.ebi.ac.uk/pdbsum/4jaj PDBsum]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Several potent Aurora kinase inhibitors derived from 5H-benzo[c][1,8]naphthyridin-6-one scaffold were identified. A crystal structure of Aurora kinase A in complex with an initial hit revealed a binding mode of the inhibitor within the ATP binding site and provided insight for structure-guided compound optimization. Subsequent SAR campaign provided a potent and selective pan Aurora inhibitor, which demonstrated potent target modulation and antiproliferative effects in the pancreatic cell line, MIAPaCa-2. Furthermore, this compound inhibited phosphorylation of histone H3 (pHH3) in mouse bone morrow upon oral administration, which is consistent with inhibition of Aurora kinase B activity.


==Function==
SAR and evaluation of novel 5H-benzo[c][1,8]naphthyridin-6-one analogs as Aurora kinase inhibitors.,Karra S, Xiao Y, Chen X, Liu-Bujalski L, Huck B, Sutton A, Goutopoulos A, Askew B, Josephson K, Jiang X, Shutes A, Shankar V, Noonan T, Garcia-Berrios G, Dong R, Dhanabal M, Tian H, Wang Z, Clark A, Goodstal S Bioorg Med Chem Lett. 2013 May 15;23(10):3081-7. doi: 10.1016/j.bmcl.2013.03.008., Epub 2013 Mar 13. PMID:23570792<ref>PMID:23570792</ref>
[[http://www.uniprot.org/uniprot/AURKA_HUMAN AURKA_HUMAN]] Mitotic serine/threonine kinases that contributes to the regulation of cell cycle progression. Associates with the centrosome and the spindle microtubules during mitosis and plays a critical role in various mitotic events including the establishment of mitotic spindle, centrosome duplication, centrosome separation as well as maturation, chromosomal alignment, spindle assembly checkpoint, and cytokinesis. Required for initial activation of CDK1 at centrosomes. Phosphorylates numerous target proteins, including ARHGEF2, BORA, BRCA1, CDC25B, DLGP5, HDAC6, KIF2A, LATS2, NDEL1, PARD3, PPP1R2, PLK1, RASSF1, TACC3, p53/TP53 and TPX2. Regulates KIF2A tubulin depolymerase activity. Required for normal axon formation. Plays a role in microtubule remodeling during neurite extension. Important for microtubule formation and/or stabilization. Also acts as a key regulatory component of the p53/TP53 pathway, and particularly the checkpoint-response pathways critical for oncogenic transformation of cells, by phosphorylating and stabilizing p53/TP53. Phosphorylates its own inhibitors, the protein phosphatase type 1 (PP1) isoforms, to inhibit their activity. Necessary for proper cilia disassembly prior to mitosis.<ref>PMID:9606188</ref> <ref>PMID:11039908</ref> <ref>PMID:11551964</ref> <ref>PMID:12390251</ref> <ref>PMID:13678582</ref> <ref>PMID:14523000</ref> <ref>PMID:15147269</ref> <ref>PMID:14990569</ref> <ref>PMID:15128871</ref> <ref>PMID:14702041</ref> <ref>PMID:15987997</ref> <ref>PMID:18056443</ref> <ref>PMID:17604723</ref> <ref>PMID:17360485</ref> <ref>PMID:18615013</ref> <ref>PMID:19812038</ref> <ref>PMID:19351716</ref> <ref>PMID:19668197</ref> <ref>PMID:19357306</ref> <ref>PMID:20643351</ref> <ref>PMID:17125279</ref>


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[4jaj]] 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=4JAJ OCA].
</div>


==Reference==
==See Also==
<ref group="xtra">PMID:023570792</ref><references group="xtra"/><references/>
*[[Serine/threonine protein kinase|Serine/threonine protein kinase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Goutopoulos, A.]]
[[Category: Goutopoulos, A]]
[[Category: Huck, B.]]
[[Category: Huck, B]]
[[Category: Jiang, X.]]
[[Category: Jiang, X]]
[[Category: Josephson, K.]]
[[Category: Josephson, K]]
[[Category: Karra, S.]]
[[Category: Karra, S]]
[[Category: Atp-binding]]
[[Category: Atp-binding]]
[[Category: Cell cycle]]
[[Category: Cell cycle]]

Revision as of 12:53, 21 December 2014

Crystal Structure of Aurora Kinase A in complex with BENZO[C][1,8]NAPHTHYRIDIN-6(5H)-ONE

4jaj, resolution 2.70Å

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