3m11: Difference between revisions

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-[[Image:3m11.jpg|left|200px]]
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+==Crystal Structure of Aurora A Kinase complexed with inhibitor==
-The line below this paragraph, containing "STRUCTURE_3m11", creates the "Structure Box" on the page.
+<StructureSection load='3m11' size='340' side='right'caption='[[3m11]], [[Resolution|resolution]] 2.75&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'>[[3m11]] 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=3M11 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3M11 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]] 2.75&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AKI:1-(4-{2-[(5,6-DIPHENYLFURO[2,3-D]PYRIMIDIN-4-YL)AMINO]ETHYL}PHENYL)-3-PHENYLUREA'>AKI</scene></td></tr>
-{{STRUCTURE_3m11|  PDB=3m11  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3m11 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3m11 OCA], [https://pdbe.org/3m11 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3m11 RCSB], [https://www.ebi.ac.uk/pdbsum/3m11 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3m11 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[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>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+A focused library of furanopyrimidine (350 compounds) was rapidly synthesized in parallel reactors and in situ screened for Aurora and epidermal growth factor receptor (EGFR) kinase activity, leading to the identification of some interesting hits. On the basis of structural biology observations, the hit 1a was modified to better fit the back pocket, producing the potent Aurora inhibitor 3 with submicromolar antiproliferative activity in HCT-116 colon cancer cell line. On the basis of docking studies with EGFR hit 1s, introduction of acrylamide Michael acceptor group led to 8, which inhibited both the wild and mutant EGFR kinase and also showed antiproliferative activity in HCC827 lung cancer cell line. Furthermore, the X-ray cocrystal study of 3 and 8 in complex with Aurora and EGFR, respectively, confirmed their hypothesized binding modes. Library construction, in situ screening, and structure-based drug design (SBDD) strategy described here could be applied for the lead identification of other kinases.
-===Crystal Structure of Aurora A Kinase complexed with inhibitor===
+Fast-forwarding hit to lead: aurora and epidermal growth factor receptor kinase inhibitor lead identification.,Coumar MS, Chu CY, Lin CW, Shiao HY, Ho YL, Reddy R, Lin WH, Chen CH, Peng YH, Leou JS, Lien TW, Huang CT, Fang MY, Wu SH, Wu JS, Chittimalla SK, Song JS, Hsu JT, Wu SY, Liao CC, Chao YS, Hsieh HP J Med Chem. 2010 Jul 8;53(13):4980-8. PMID:20550212<ref>PMID:20550212</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3m11" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_20550212}}, adds the Publication Abstract to the page
+*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 20550212 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_20550212}}
+__TOC__
+</StructureSection>
-==About this Structure==
-[[3m11]] 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=3M11 OCA].
-==Reference==
-<ref group="xtra">PMID:20550212</ref><references group="xtra"/>
 [[Category: Homo sapiens]]
-[[Category: Non-specific serine/threonine protein kinase]]
+[[Category: Large Structures]]
-[[Category: Coumar, M S.]]
+[[Category: Coumar MS]]
-[[Category: Hsieh, H P.]]
+[[Category: Hsieh HP]]
-[[Category: Leou, J S.]]
+[[Category: Leou JS]]
-[[Category: Wu, J S.]]
+[[Category: Wu JS]]
-[[Category: Wu, S Y.]]
+[[Category: Wu SY]]