View source for 5osk


==Tubulin-7j complex==
<StructureSection load='5osk' size='340' side='right'caption='[[5osk]], [[Resolution|resolution]] 2.11&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5osk]] 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=5OSK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5OSK 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]] 2.11&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A9Q:3-(2,5-Dimethoxybenzyl)-7-sulfamoyloxy-6-methoxy-3,4-dihydroquinazolin-2(1H)-one'>A9Q</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=IMD:IMIDAZOLE'>IMD</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=5osk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5osk OCA], [https://pdbe.org/5osk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5osk RCSB], [https://www.ebi.ac.uk/pdbsum/5osk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5osk 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 ==
Quinazolinone-based anti-cancer agents were designed, decorated with functional groups from a 2-methoxyestradiol-based microtubule disruptor series, incorporating the aryl sulfamate motif of steroid sulfatase (STS) inhibitors. The steroidal AB-ring system was mimicked, favoring conformations with an N-2 substituent occupying D-ring space. Evaluation against breast and prostate tumor cell lines identified 7b with DU-145 anti-proliferative activity (GI50 300 nM). A preliminary structure-activity relationship afforded compounds (e.g. 7j GI50 50 nM) with activity exceeding that of the parent. Both 7b and 7j inhibit tubulin assembly in vitro and colchicine binding and 7j was successfully co-crystallized with the alphabeta-tubulin heterodimer as the first of its class, its sulfamate group interacting positively at the colchicine binding site. Microtubule destabilization by 7j likely prevents the curved-to-straight conformational transition. Quinazolinone sulfamates surprisingly showed weak STS inhibition. Preliminary in vivo studies in a multiple myeloma xenograft model for 7b showed oral activity, confirming the promise of this template.

Quinazolinone-based Anticancer Agents: Synthesis, Anti-proliferative SAR, Anti-tubulin Activity and Tubulin Co-crystal Structure.,Dohle W, Jourdan FL, Menchon G, Prota AE, Foster PA, Mannion P, Hamel E, Thomas MP, Kasprzyk PG, Ferrandis E, Steinmetz MO, Leese MP, Potter BVL J Med Chem. 2017 Dec 11. doi: 10.1021/acs.jmedchem.7b01474. PMID:29227648<ref>PMID:29227648</ref>

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

==See Also==
*[[Stathmin-4 3D structures|Stathmin-4 3D structures]]
*[[Tubulin 3D Structures|Tubulin 3D Structures]]
*[[Tubulin tyrosine ligase|Tubulin tyrosine ligase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bos taurus]]
[[Category: Gallus gallus]]
[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Menchon G]]
[[Category: Potter BVL]]
[[Category: Prota AE]]
[[Category: Steinmetz MO]]