2bmc
From Proteopedia
(Difference between revisions)
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<StructureSection load='2bmc' size='340' side='right'caption='[[2bmc]], [[Resolution|resolution]] 2.60Å' scene=''> | <StructureSection load='2bmc' size='340' side='right'caption='[[2bmc]], [[Resolution|resolution]] 2.60Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[2bmc]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/ | + | <table><tr><td colspan='2'>[[2bmc]] is a 6 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=2BMC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BMC 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]] 2.6Å</td></tr> |
| - | <tr id=' | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MPY:(3E)-N-(2,6-DIETHYLPHENYL)-3-{[4-(4-METHYLPIPERAZIN-1-YL)BENZOYL]IMINO}PYRROLO[3,4-C]PYRAZOLE-5(3H)-CARBOXAMIDE'>MPY</scene></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=2bmc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bmc OCA], [https://pdbe.org/2bmc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bmc RCSB], [https://www.ebi.ac.uk/pdbsum/2bmc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bmc 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=2bmc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bmc OCA], [https://pdbe.org/2bmc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bmc RCSB], [https://www.ebi.ac.uk/pdbsum/2bmc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bmc ProSAT]</span></td></tr> | ||
</table> | </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> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2bmc ConSurf]. | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2bmc ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | Potent and selective Aurora kinase inhibitors were identified from the combinatorial expansion of the 1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole bi-cycle, a novel and versatile scaffold designed to target the ATP pocket of protein kinases. The most potent compound reported in this study had an IC(50) of 0.027 microM in the enzymatic assay for Aur-A inhibition and IC(50)s between 0.05 microM and 0.5 microM for the inhibition of proliferation of different tumor cell lines. | ||
| - | |||
| - | Potent and selective Aurora inhibitors identified by the expansion of a novel scaffold for protein kinase inhibition.,Fancelli D, Berta D, Bindi S, Cameron A, Cappella P, Carpinelli P, Catana C, Forte B, Giordano P, Giorgini ML, Mantegani S, Marsiglio A, Meroni M, Moll J, Pittala V, Roletto F, Severino D, Soncini C, Storici P, Tonani R, Varasi M, Vulpetti A, Vianello P J Med Chem. 2005 Apr 21;48(8):3080-4. PMID:15828847<ref>PMID:15828847</ref> | ||
| - | |||
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 2bmc" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Homo sapiens]] |
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | + | [[Category: Berta D]] | |
| - | [[Category: Berta | + | [[Category: Bindi S]] |
| - | [[Category: Bindi | + | [[Category: Cameron AD]] |
| - | [[Category: Cameron | + | [[Category: Catana C]] |
| - | [[Category: Catana | + | [[Category: Fancelli D]] |
| - | [[Category: Fancelli | + | [[Category: Forte B]] |
| - | [[Category: Forte | + | [[Category: Giordano P]] |
| - | [[Category: Giordano | + | [[Category: Izzo G]] |
| - | [[Category: Izzo | + | [[Category: Mantegani S]] |
| - | [[Category: Mantegani | + | [[Category: Meroni M]] |
| - | [[Category: Meroni | + | [[Category: Moll J]] |
| - | [[Category: Moll | + | [[Category: Pittala V]] |
| - | [[Category: Pittala | + | [[Category: Rusconi L]] |
| - | [[Category: Rusconi | + | [[Category: Sagliano A]] |
| - | [[Category: Sagliano | + | [[Category: Severino D]] |
| - | [[Category: Severino | + | [[Category: Storici P]] |
| - | [[Category: Storici | + | [[Category: Tonani R]] |
| - | [[Category: Tonani | + | [[Category: Varasi M]] |
| - | [[Category: Varasi | + | [[Category: Vianello P]] |
| - | [[Category: Vianello | + | [[Category: Vulpetti A]] |
| - | [[Category: Vulpetti | + | |
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Current revision
Aurora-2 T287D T288D complexed with PHA-680632
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Categories: Homo sapiens | Large Structures | Berta D | Bindi S | Cameron AD | Catana C | Fancelli D | Forte B | Giordano P | Izzo G | Mantegani S | Meroni M | Moll J | Pittala V | Rusconi L | Sagliano A | Severino D | Storici P | Tonani R | Varasi M | Vianello P | Vulpetti A
