6fii | pdb_00006fii

Tubulin-Spongistatin complex

spinqualitylabelsall models 6fii, resolution 2.41Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6fii is a 6 chain structure with sequence from Bos taurus, Buffalo rat and Chick. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ACP, CA, DMS, GDP, GOL, GTP, MES, MG, SG9 Gene: Stmn4 (Buffalo rat), TTL (CHICK) 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. [STMN4_RAT] Exhibits microtubule-destabilizing activity. [TBB2B_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 (By similarity). Publication Abstract from PubMed Microtubule-targeting agents (MTAs) like taxol and vinblastine are among the most successful chemotherapeutic drugs against cancer. Here, we describe a fluorescence anisotropy-based assay that specifically probes for ligands targeting the recently discovered maytansine site of tubulin. Using this assay, we have determined the dissociation constants of known maytansine site ligands, including the pharmacologically active degradation product of the clinical antibody-drug conjugate trastuzumab emtansine. In addition, we discovered that the two natural products spongistatin-1 and disorazole Z with established cellular potency bind to the maytansine site on beta-tubulin. The high-resolution crystal structures of spongistatin-1 and disorazole Z in complex with tubulin allowed the definition of an additional sub-site adjacent to the pocket shared by all maytansine-site ligands, which could be exploitable as a distinct, separate target site for small molecules. Our study provides a basis for the discovery and development of next-generation MTAs for the treatment of cancer. A fluorescence anisotropy assay to discover and characterize ligands targeting the maytansine site of tubulin.,Menchon G, Prota AE, Lucena-Agell D, Bucher P, Jansen R, Irschik H, Muller R, Paterson I, Diaz JF, Altmann KH, Steinmetz MO Nat Commun. 2018 May 29;9(1):2106. doi: 10.1038/s41467-018-04535-8. PMID:29844393 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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