View source for 5jvd


==Tubulin-TUB092 complex==
<StructureSection load='5jvd' size='340' side='right'caption='[[5jvd]], [[Resolution|resolution]] 2.39&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5jvd]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus], [https://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JVD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5JVD 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]] 2.393&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6NL:(2E)-3-(3-HYDROXY-4-METHOXYPHENYL)-1-(7-METHOXY-2H-1,3-BENZODIOXOL-5-YL)-2-METHYLPROP-2-EN-1-ONE'>6NL</scene>, <scene name='pdbligand=ACP:PHOSPHOMETHYLPHOSPHONIC+ACID+ADENYLATE+ESTER'>ACP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=5jvd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jvd OCA], [https://pdbe.org/5jvd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5jvd RCSB], [https://www.ebi.ac.uk/pdbsum/5jvd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5jvd ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TBA1B_BOVIN TBA1B_BOVIN] Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
We investigated the microtubule-destabilizing, vascular-targeting, anti-tumor and anti-metastatic activities of a new series of chalcones, whose prototype compound is (E)-3-(3''-amino-4''-methoxyphenyl)-1-(5'-methoxy-3',4'-methylendioxyphenyl)-2-me thylprop-2-en-1-one (TUB091). X-ray crystallography showed that these chalcones bind to the colchicine site of tubulin and therefore prevent the curved-to-straight structural transition of tubulin, which is required for microtubule formation. Accordingly, TUB091 inhibited cancer and endothelial cell growth, induced G2/M phase arrest and apoptosis at 1-10 nM. In addition, TUB091 displayed vascular disrupting effects in vitro and in the chicken chorioallantoic membrane (CAM) assay at low nanomolar concentrations. A water-soluble L-Lys-L-Pro derivative of TUB091 (i.e. TUB099) showed potent antitumor activity in melanoma and breast cancer xenograft models by causing rapid intratumoral vascular shutdown and massive tumor necrosis. TUB099 also displayed anti-metastatic activity similar to that of combretastatin A4-phosphate. Our data indicate that this novel class of chalcones represents interesting lead molecules for the design of vascular disrupting agents (VDAs). Moreover, we provide evidence that our prodrug approach may be valuable for the development of anti-cancer drugs.

Antivascular and antitumor properties of the tubulin-binding chalcone TUB091.,Canela MD, Noppen S, Bueno O, Prota AE, Bargsten K, Saez-Calvo G, Jimeno ML, Benkheil M, Ribatti D, Velazquez S, Camarasa MJ, Diaz JF, Steinmetz MO, Priego EM, Perez-Perez MJ, Liekens S Oncotarget. 2016 May 20. doi: 10.18632/oncotarget.9527. PMID:27224920<ref>PMID:27224920</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5jvd" style="background-color:#fffaf0;"></div>

==See Also==
*[[Stathmin-4 3D structures|Stathmin-4 3D structures]]
*[[Tubulin 3D Structures|Tubulin 3D Structures]]
*[[Tubulin tyrosine ligase 3D structures|Tubulin tyrosine ligase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bos taurus]]
[[Category: Gallus gallus]]
[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Bargsten K]]
[[Category: Benkheil M]]
[[Category: Bueno O]]
[[Category: Camarasa M-J]]
[[Category: Canela M-D]]
[[Category: Diaz JF]]
[[Category: Jimeno M-L]]
[[Category: Liekens S]]
[[Category: Noppen S]]
[[Category: Perez-Perez M-J]]
[[Category: Priego E-M]]
[[Category: Prota AE]]
[[Category: Ribatti D]]
[[Category: Saez-Calvo G]]
[[Category: Steinmetz MO]]
[[Category: Velazquez S]]