5FNV

a new complex structure of tubulin with an alpha-beta unsaturated lactone

5FNV の概要

• エントリーDOI: 10.2210/pdb5fnv/pdb
• 分子名称: TUBULIN ALPHA-1B CHAIN, PIRONETIN, PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER, ... (12 entities in total)
• 機能のキーワード: structural protein, tubulin complex alpha-beta unsaturated lactone
• 由来する生物種: GALLUS GALLUS (CHICKEN); 詳細
• 細胞内の位置: Cytoplasm, cytoskeleton: Q2XVP4 P02554; Golgi apparatus : P63043
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 264899.44

構造登録者

Wang, Y.,Naismith, J.,Zhu, X. (登録日: 2015-11-16, 公開日: 2016-05-18, 最終更新日: 2024-10-23)

主引用文献

Yang, J.,Wang, Y.,Wang, T.,Jiang, J.,Botting, C.H.,Liu, H.,Chen, Q.,Yang, J.,Naismith, J.H.,Zhu, X.,Chen, L.
Pironetin Reacts Covalently with Cysteine-316 of Alpha-Tubulin to Destabilize Microtubule.
Nat.Commun., 7:12103-, 2016

PubMed Abstract: Molecules that alter the normal dynamics of microtubule assembly and disassembly include many anticancer drugs in clinical use. So far all such therapeutics target β-tubulin, and structural biology has explained the basis of their action and permitted design of new drugs. However, by shifting the profile of β-tubulin isoforms, cancer cells become resistant to treatment. Compounds that bind to α-tubulin are less well characterized and unexploited. The natural product pironetin is known to bind to α-tubulin and is a potent inhibitor of microtubule polymerization. Previous reports had identified that pironetin reacts with lysine-352 residue however analogues designed on this model had much lower potency, which was difficult to explain, hindering further development. We report crystallographic and mass spectrometric data that reveal that pironetin forms a covalent bond to cysteine-316 in α-tubulin via a Michael addition reaction. These data provide a basis for the rational design of α-tubulin targeting chemotherapeutics.

PubMed: 27357539
DOI: 10.1038/NCOMMS12103

実験手法

X-RAY DIFFRACTION (2.61 Å)