5XLT

The crystal structure of tubulin in complex with 4'-demethylepipodophyllotoxin

5XLT の概要

• エントリーDOI: 10.2210/pdb5xlt/pdb
• 分子名称: Tubulin alpha-1B chain, (5S,5aR,8aR,9R)-9-(3,5-dimethoxy-4-oxidanyl-phenyl)-5-oxidanyl-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[6,5-f][1,3]benzodioxol-8-one, PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER, ... (12 entities in total)
• 機能のキーワード: tubulin, inhibitor, cell cycle
• 由来する生物種: Rattus norvegicus (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: 265111.56

構造登録者

Yu, Y.,Chen, Q. (登録日: 2017-05-11, 公開日: 2017-09-27, 最終更新日: 2024-03-27)

主引用文献

Niu, L.,Wang, Y.,Wang, C.,Wang, Y.,Jiang, X.,Ma, L.,Wu, C.,Yu, Y.,Chen, Q.
Structure of 4'-demethylepipodophyllotoxin in complex with tubulin provides a rationale for drug design
Biochem. Biophys. Res. Commun., 493:718-722, 2017

PubMed Abstract: Microtubules consists of αβ-tubulin heterodimers and are highly attractive targets for anti-cancer drugs. A broad range of agents have been identified to bind to tubulin and interfere with microtubule assembly, including colchicine binding site inhibitors (CBSIs). Podophyllotoxin is a CBSI that inhibits the assembly of microtubules. However, for a long time, the design and development of podophyllotoxin family drugs have been hindered by the lack of high-resolution structural information of the tubulin-agent complex. We report the first high-resolution (2.8 Å) structure of a podophyllotoxin family agent (4'-demethylepipodophyllotoxin, DMEP) complexed with tubulin and revealed the detailed interactions between DMEP and tubulin. Comparison of this structure and other CBSIs explains previous results of the structure-activity-relationship (SAR) studies, and provides insights into the development of new podophyllotoxin derivatives targeting the colchicine site.

PubMed: 28864414
DOI: 10.1016/j.bbrc.2017.08.125

実験手法

X-RAY DIFFRACTION (2.813 Å)