7EN3

Crystal structure of tubulin in complex with Tubulysin analogue TGL

7EN3 の概要

• エントリーDOI: 10.2210/pdb7en3/pdb
• 分子名称: Tubulin alpha-1B chain, (2S,4R)-5-(4-fluorophenyl)-2-methyl-4-[[2-[(1R,3R)-4-methyl-3-[5-methylhexyl-[(2S,3S)-3-methyl-2-[[(2R)-1-methylpiperidin-2-yl]carbonylamino]pentanoyl]amino]-1-oxidanyl-pentyl]-1,3-thiazol-4-yl]carbonylamino]pentanoic acid, PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER, ... (12 entities in total)
• 機能のキーワード: microtubule assembly inhibitors, structural protein-inhibitor complex, structural protein/inhibitor
• 由来する生物種: Sus scrofa (Pig); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 265622.38

構造登録者

Wang, Y.,Li, W. (登録日: 2021-04-15, 公開日: 2022-04-27, 最終更新日: 2023-11-29)

主引用文献

Li, W.,Tan, L.,Zhang, Z.,Xia, Q.,Lei, D.,Li, Y.,Zhang, T.,Zeng, S.,Sima, X.,Wang, Y.
The X-ray structure of tubulysin analogue TGL in complex with tubulin and three possible routes for the development of next-generation tubulysin analogues.
Biochem.Biophys.Res.Commun., 565:29-35, 2021

PubMed Abstract: Microtubule-targeting agents (MTAs) are the most commonly used anti-cancer drugs. At least fourteen microtubule inhibitors and ten antibody drug conjugates (ADCs) linking MTAs are approved by FDA for clinical use in cancer therapy. In current research, we determined the crystal structure of tubulysin analogue TGL in complex with tubulin at a high resolution (2.65 Å). In addition, we summarized all of the previously published high-resolution crystal structures of ligands in the vinca site to provide structural insights for the rational design of the new vinca-site ligands. Moreover, based on the aligned results of the vinca site ligands, we provided three possible routes for designing new tubulysin analogues, namely macrocyclization between the N-14 side chain and the N-9 side chain, the hybird of tubulysin M and phomopsin A, and growing new aryl group at C-21. These designed structures will inspire the development of new MTAs or payloads in cancer therapy.

PubMed: 34090207
DOI: 10.1016/j.bbrc.2021.05.086

実験手法

X-RAY DIFFRACTION (2.643 Å)