6vpm

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Current revision (09:15, 9 October 2024) (edit) (undo)
 
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<StructureSection load='6vpm' size='340' side='right'caption='[[6vpm]], [[Resolution|resolution]] 1.58&Aring;' scene=''>
<StructureSection load='6vpm' size='340' side='right'caption='[[6vpm]], [[Resolution|resolution]] 1.58&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[6vpm]] is a 2 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=6VPM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VPM FirstGlance]. <br>
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<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VPM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VPM FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.58&#8491;</td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.58&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MLA:MALONIC+ACID'>MLA</scene>, <scene name='pdbligand=R74:N~2~-[(2H-1,3-benzodioxol-5-yl)acetyl]-N-[(pyridin-4-yl)methyl]-L-cysteinamide'>R74</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MLA:MALONIC+ACID'>MLA</scene>, <scene name='pdbligand=R74:N~2~-[(2H-1,3-benzodioxol-5-yl)acetyl]-N-[(pyridin-4-yl)methyl]-L-cysteinamide'>R74</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</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=6vpm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vpm OCA], [https://pdbe.org/6vpm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vpm RCSB], [https://www.ebi.ac.uk/pdbsum/6vpm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vpm 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=6vpm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vpm OCA], [https://pdbe.org/6vpm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vpm RCSB], [https://www.ebi.ac.uk/pdbsum/6vpm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vpm ProSAT]</span></td></tr>
</table>
</table>
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== Function ==
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<div style="background-color:#fffaf0;">
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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> [https://www.uniprot.org/uniprot/TPX2_HUMAN TPX2_HUMAN] Spindle assembly factor. Required for normal assembly of mitotic spindles. Required for normal assembly of microtubules during apoptosis. Required for chromatin and/or kinetochore dependent microtubule nucleation. Mediates AURKA localization to spindle microtubules. Activates AURKA by promoting its autophosphorylation at 'Thr-288' and protects this residue against dephosphorylation.<ref>PMID:18663142</ref> <ref>PMID:19208764</ref>
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== Publication Abstract from PubMed ==
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Cell cycle-dependent redox changes can mediate transient covalent modifications of cysteine thiols to modulate the activities of regulatory kinases and phosphatases. Our previously reported finding that protein cysteine oxidation is increased during mitosis relative to other cell cycle phases suggests that redox modifications could play prominent roles in regulating mitotic processes. The Aurora family of kinases and their downstream targets are key components of the cellular machinery that ensures the proper execution of mitosis and the accurate segregation of chromosomes to daughter cells. In this study, x-ray crystal structures of the Aurora A kinase domain delineate redox-sensitive cysteine residues that, upon covalent modification, can allosterically regulate kinase activity and oligomerization state. We showed in both Xenopus laevis egg extracts and mammalian cells that a conserved cysteine residue within the Aurora A activation loop is crucial for Aurora A activation by autophosphorylation. We further showed that covalent disulfide adducts of this residue promote autophosphorylation of the Aurora A kinase domain. These findings reveal a potential mechanistic link between Aurora A activation and changes in the intracellular redox state during mitosis and provide insights into how novel small-molecule inhibitors may be developed to target specific subpopulations of Aurora A.
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Redox priming promotes Aurora A activation during mitosis.,Lim DC, Joukov V, Rettenmaier TJ, Kumagai A, Dunphy WG, Wells JA, Yaffe MB Sci Signal. 2020 Jul 21;13(641). pii: 13/641/eabb6707. doi:, 10.1126/scisignal.abb6707. PMID:32694171<ref>PMID:32694171</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 6vpm" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Homo sapiens]]
 
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Lim DC]]
[[Category: Lim DC]]
[[Category: Yaffe MB]]
[[Category: Yaffe MB]]

Current revision

TPX2 residues 7-20 fused to Aurora A residues 116-389 with C290 disulfide bonded to compound 8-34, and in complex with AMP-PNP

PDB ID 6vpm

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