5SBE

Tubulin-maytansinoid-5c-complex

5SBE の概要

• エントリーDOI: 10.2210/pdb5sbe/pdb
• Group deposition: T2R-TTL-maytansinoid structures (G_1002215)
• 分子名称: Tubulin alpha-1B chain, (1S,2R,3S,5S,6S,16E,18E,20R)-11-chloro-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.1~10,14~.0~3,5~]hexacosa-10(26),11,13,16,18,21-hexaen-6-yl hept-6-ynoate, PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER, ... (12 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 (Rat); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 265161.47

構造登録者

Marzullo, P.,Boiarska, Z.,Perez-Pena, H.,Abel, A.-C.,Alvarez-Bernad, B.,Lucena-Agell, D.,Vasile, F.,Sironi, M.,Steinmetz, M.O.,Prota, A.E.,Diaz, J.F.,Pieraccini, S.,Passarella, D. (登録日: 2021-07-20, 公開日: 2021-12-08, 最終更新日: 2024-05-22)

主引用文献

Marzullo, P.,Boiarska, Z.,Perez-Pena, H.,Abel, A.C.,Alvarez-Bernad, B.,Lucena-Agell, D.,Vasile, F.,Sironi, M.,Altmann, K.H.,Prota, A.E.,Diaz, J.F.,Pieraccini, S.,Passarella, D.
Maytansinol Derivatives: Side Reactions as a Chance for New Tubulin Binders.
Chemistry, 28:e202103520-e202103520, 2022

PubMed Abstract: Maytansinol is a valuable precursor for the preparation of maytansine derivatives (known as maytansinoids). Inspired by the intriguing structure of the macrocycle and the success in targeted cancer therapy of the derivatives, we explored the maytansinol acylation reaction. As a result, we were able to obtain a series of derivatives with novel modifications of the maytansine scaffold. We characterized these molecules by docking studies, by a comprehensive biochemical evaluation, and by determination of their crystal structures in complex with tubulin. The results shed further light on the intriguing chemical behavior of maytansinoids and confirm the relevance of this peculiar scaffold in the scenario of tubulin binders.

PubMed: 34788896
DOI: 10.1002/chem.202103520

実験手法

X-RAY DIFFRACTION (2.75 Å)