3d14: Difference between revisions
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<StructureSection load='3d14' size='340' side='right'caption='[[3d14]], [[Resolution|resolution]] 1.90Å' scene=''> | <StructureSection load='3d14' size='340' side='right'caption='[[3d14]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3d14]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[3d14]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3D14 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3D14 FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AK1:1-{5-[2-(THIENO[3,2-D]PYRIMIDIN-4-YLAMINO)ETHYL]-1,3-THIAZOL-2-YL}-3-[3-(TRIFLUOROMETHYL)PHENYL]UREA'>AK1</scene></td></tr> | |||
<tr id=' | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3d14 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3d14 OCA], [https://pdbe.org/3d14 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3d14 RCSB], [https://www.ebi.ac.uk/pdbsum/3d14 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3d14 ProSAT]</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=3d14 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3d14 OCA], [https://pdbe.org/3d14 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3d14 RCSB], [https://www.ebi.ac.uk/pdbsum/3d14 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3d14 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/AURKA_MOUSE AURKA_MOUSE] 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:9245792</ref> <ref>PMID:19075002</ref> <ref>PMID:19668197</ref> <ref>PMID:20643351</ref> | |||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Mus musculus]] | ||
[[Category: Allen DA]] | |||
[[Category: Allen | [[Category: Baskaran S]] | ||
[[Category: Baskaran | [[Category: Elling RA]] | ||
[[Category: Elling | [[Category: Oslob JD]] | ||
[[Category: Oslob | [[Category: Romanowski MJ]] | ||
[[Category: Romanowski | |||
Latest revision as of 15:37, 30 August 2023
Crystal structure of mouse Aurora A (Asn186->Gly, Lys240->Arg, Met302->Leu) in complex with 1-{5-[2-(thieno[3,2-d]pyrimidin-4-ylamino)-ethyl]- thiazol-2-yl}-3-(3-trifluoromethyl-phenyl)-ureaCrystal structure of mouse Aurora A (Asn186->Gly, Lys240->Arg, Met302->Leu) in complex with 1-{5-[2-(thieno[3,2-d]pyrimidin-4-ylamino)-ethyl]- thiazol-2-yl}-3-(3-trifluoromethyl-phenyl)-urea
Structural highlights
FunctionAURKA_MOUSE 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.[1] [2] [3] [4] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThis communication describes the discovery of a novel series of Aurora kinase inhibitors. Key SAR and critical binding elements are discussed. Some of the more advanced analogues potently inhibit cellular proliferation and induce phenotypes consistent with Aurora kinase inhibition. In particular, compound 21 (SNS-314) is a potent and selective Aurora kinase inhibitor that exhibits significant activity in pre-clinical in vivo tumor models. Discovery of a potent and selective aurora kinase inhibitor.,Oslob JD, Romanowski MJ, Allen DA, Baskaran S, Bui M, Elling RA, Flanagan WM, Fung AD, Hanan EJ, Harris S, Heumann SA, Hoch U, Jacobs JW, Lam J, Lawrence CE, McDowell RS, Nannini MA, Shen W, Silverman JA, Sopko MM, Tangonan BT, Teague J, Yoburn JC, Yu CH, Zhong M, Zimmerman KM, O'Brien T, Lew W Bioorg Med Chem Lett. 2008 Sep 1;18(17):4880-4. Epub 2008 Jul 24. PMID:18678489[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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