4I4T

Crystal structure of tubulin-RB3-TTL-Zampanolide complex

4I4T の概要

• エントリーDOI: 10.2210/pdb4i4t/pdb
• 関連するPDBエントリー: 4I4T 4I50 4I55 4IHJ 4IIJ
• 分子名称: Tubulin alpha-1B chain, GUANOSINE-5'-DIPHOSPHATE, TYROSINE, ... (15 entities in total)
• 機能のキーワード: alpha-tubulin, beta-tubulin, ligase, gtpase, stathmin, zamanolide, cell cycle
• 由来する生物種: Rattus norvegicus (brown rat,rat,rats); 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: 265603.25

構造登録者

Prota, A.E.,Steinmetz, M.O. (登録日: 2012-11-28, 公開日: 2013-01-23, 最終更新日: 2024-11-20)

主引用文献

Prota, A.E.,Bargsten, K.,Zurwerra, D.,Field, J.J.,Diaz, J.F.,Altmann, K.H.,Steinmetz, M.O.
Molecular Mechanism of Action of Microtubule-Stabilizing Anticancer Agents.
Science, 339:587-590, 2013

PubMed Abstract: Microtubule-stabilizing agents (MSAs) are efficacious chemotherapeutic drugs widely used for the treatment of cancer. Despite the importance of MSAs for medical applications and basic research, their molecular mechanisms of action on tubulin and microtubules remain elusive. We determined high-resolution crystal structures of αβ-tubulin in complex with two unrelated MSAs, zampanolide and epothilone A. Both compounds were bound to the taxane pocket of β-tubulin and used their respective side chains to induce structuring of the M-loop into a short helix. Because the M-loop establishes lateral tubulin contacts in microtubules, these findings explain how taxane-site MSAs promote microtubule assembly and stability. Further, our results offer fundamental structural insights into the control mechanisms of microtubule dynamics.

PubMed: 23287720
DOI: 10.1126/science.1230582

実験手法

X-RAY DIFFRACTION (1.8 Å)