3k5u

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[[Image:3k5u.png|left|200px]]
 
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==Identification, SAR Studies and X-ray Cocrystal Analysis of a Novel Furano-pyrimidine Aurora Kinase A Inhibitor==
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The line below this paragraph, containing "STRUCTURE_3k5u", creates the "Structure Box" on the page.
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<StructureSection load='3k5u' size='340' side='right'caption='[[3k5u]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[3k5u]] 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=3K5U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3K5U FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.35&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PFQ:2-[(5,6-DIPHENYLFURO[2,3-D]PYRIMIDIN-4-YL)AMINO]ETHANOL'>PFQ</scene></td></tr>
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{{STRUCTURE_3k5u| PDB=3k5u | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3k5u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3k5u OCA], [https://pdbe.org/3k5u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3k5u RCSB], [https://www.ebi.ac.uk/pdbsum/3k5u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3k5u ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://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>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Herein we reveal a simple method for the identification of novel Aurora kinase A inhibitors through substructure searching of an in-house compound library to select compounds for testing. A hydrazone fragment conferring Aurora kinase activity and heterocyclic rings most frequently reported in kinase inhibitors were used as substructure queries to filter the in-house compound library collection prior to testing. Five new series of Aurora kinase inhibitors were identified through this strategy, with IC(50) values ranging from approximately 300 nM to approximately 15 microM, by testing only 133 compounds from a database of approximately 125,000 compounds. Structure-activity relationship studies and X-ray co-crystallographic analysis of the most potent compound, a furanopyrimidine derivative with an IC(50) value of 309 nM toward Aurora kinase A, were carried out. The knowledge gained through these studies could help in the future design of potent Aurora kinase inhibitors.
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===Identification, SAR Studies and X-ray Cocrystal Analysis of a Novel Furano-pyrimidine Aurora Kinase A Inhibitor===
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Identification, SAR studies, and X-ray co-crystallographic analysis of a novel furanopyrimidine aurora kinase A inhibitor.,Coumar MS, Tsai MT, Chu CY, Uang BJ, Lin WH, Chang CY, Chang TY, Leou JS, Teng CH, Wu JS, Fang MY, Chen CH, Hsu JT, Wu SY, Chao YS, Hsieh HP ChemMedChem. 2010 Feb 1;5(2):255-67. PMID:20039358<ref>PMID:20039358</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 3k5u" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_20039358}}, adds the Publication Abstract to the page
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*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 20039358 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_20039358}}
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__TOC__
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</StructureSection>
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==About this Structure==
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[[3k5u]] 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=3K5U OCA].
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==Reference==
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<ref group="xtra">PMID:20039358</ref><ref group="xtra">PMID:19140666</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Non-specific serine/threonine protein kinase]]
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[[Category: Large Structures]]
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[[Category: Coumar, M S.]]
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[[Category: Coumar MS]]
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[[Category: Hsieh, H P.]]
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[[Category: Hsieh HP]]
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[[Category: Leou, J S.]]
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[[Category: Leou JS]]
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[[Category: Wu, J S.]]
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[[Category: Wu JS]]
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[[Category: Wu, S Y.]]
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[[Category: Wu SY]]
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[[Category: Atp-binding site]]
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[[Category: Aurora kinase inhibitor]]
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[[Category: Cell cycle]]
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[[Category: Cytoskeleton]]
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[[Category: H-bonding]]
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[[Category: Kinase]]
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[[Category: Nucleotide-binding]]
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[[Category: Phosphoprotein]]
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[[Category: Serine/threonine-protein kinase]]
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[[Category: Transferase]]
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[[Category: Virtual screening]]
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[[Category: X-ray co-crystal analysis]]
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Current revision

Identification, SAR Studies and X-ray Cocrystal Analysis of a Novel Furano-pyrimidine Aurora Kinase A Inhibitor

PDB ID 3k5u

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