5ng1 | pdb_00005ng1

TUBULIN-MTC-zampanolide complex

spinqualitylabelsall models 5ng1, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5ng1 is a 6 chain structure with sequence from [1] and Bos taurus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 8WB, 8WE, ACP, CA, GDP, GOL, GTP, MES, MG, ZPN 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 The marine natural product zampanolide and analogues thereof constitute a new chemotype of taxoid site microtubule-stabilizing agents with a covalent mechanism of action. Zampanolide-ligated tubulin has the switch-activation loop (M-loop) in the assembly prone form and, thus, represents an assembly activated state of the protein. In this study, we have characterized the biochemical properties of the covalently modified, activated tubulin dimer, and we have determined the effect of zampanolide on tubulin association and the binding of tubulin ligands at other binding sites. Tubulin activation by zampanolide does not affect its longitudinal oligomerization but does alter its lateral association properties. The covalent binding of zampanolide to beta-tubulin affects both the colchicine site, causing a change of the quantum yield of the bound ligand, and the exchangeable nucleotide binding site, reducing the affinity for the nucleotide. While these global effects do not change the binding affinity of 2-methoxy-5-(2,3,4-trimethoxyphenyl)-2,4,6-cycloheptatrien-1-one (MTC) (a reversible binder of the colchicine site), the binding affinity of a fluorescent analogue of GTP (Mant-GTP) at the nucleotide E-site is reduced from 12 +/- 2 x 105 M-1 in the case of unmodified tubulin to 1.4 +/- 0.3 x 105 M-1 in the case of the zampanolide tubulin adduct, indicating signal transmission between the taxane site and the colchicine and nucleotide sites of beta-tubulin. Zampanolide Binding to Tubulin Indicates Cross-Talk of Taxane Site with Colchicine and Nucleotide Sites.,Field JJ, Pera B, Gallego JE, Calvo E, Rodriguez-Salarichs J, Saez-Calvo G, Zuwerra D, Jordi M, Andreu JM, Prota AE, Menchon G, Miller JH, Altmann KH, Diaz JF J Nat Prod. 2017 Oct 12. doi: 10.1021/acs.jnatprod.7b00704. PMID:29023132 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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