5jvd

Tubulin-TUB092 complex

spinqualitylabelsall models 5jvd, resolution 2.39Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5jvd is a 6 chain structure with sequence from Bos taurus, Gallus gallus and Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.393Å Ligands: 6NL, ACP, CA, GDP, GOL, GTP, MES, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Stathmin-4 3D structures Tubulin 3D Structures Tubulin tyrosine ligase 3D structures

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