5NFZ

TUBULIN-MTC complex

5NFZ の概要

• エントリーDOI: 10.2210/pdb5nfz/pdb
• 分子名称: Tubulin alpha-1B chain, GUANOSINE-5'-DIPHOSPHATE, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, ... (13 entities in total)
• 機能のキーワード: cell cycle, tubulin fold, cytoskeleton, microtubule
• 由来する生物種: Rattus norvegicus (Norway Rat); 詳細
• 細胞内の位置: Cytoplasm, cytoskeleton: P81947 Q6B856; Golgi apparatus : P63043
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 265243.10

構造登録者

Field, J.J.,Pera, B.,Estevez Gallego, J.,Calvo, E.,Rodriguez-Salarichs, J.,Saez-Calvo, G.,Zuwerra, D.,Jordi, M.,Prota, A.E.,Menchon, G.,Miller, J.H.,Altmann, K.-H.,Diaz, J.F. (登録日: 2017-03-16, 公開日: 2017-10-25, 最終更新日: 2024-01-17)

主引用文献

Field, J.J.,Pera, B.,Gallego, J.E.,Calvo, E.,Rodriguez-Salarichs, J.,Saez-Calvo, G.,Zuwerra, D.,Jordi, M.,Andreu, J.M.,Prota, A.E.,Menchon, G.,Miller, J.H.,Altmann, K.H.,Diaz, J.F.
Zampanolide Binding to Tubulin Indicates Cross-Talk of Taxane Site with Colchicine and Nucleotide Sites.
J. Nat. Prod., 81:494-505, 2018

PubMed Abstract: 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 β-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 × 10 M in the case of unmodified tubulin to 1.4 ± 0.3 × 10 M in the case of the zampanolide tubulin adduct, indicating signal transmission between the taxane site and the colchicine and nucleotide sites of β-tubulin.

PubMed: 29023132
DOI: 10.1021/acs.jnatprod.7b00704

実験手法

X-RAY DIFFRACTION (2.1 Å)