7ZX2

Tubulin-Pelophen B complex

7ZX2 の概要

• エントリーDOI: 10.2210/pdb7zx2/pdb
• 分子名称: Tubulin alpha-1B chain, GUANOSINE-5'-DIPHOSPHATE, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, ... (15 entities in total)
• 機能のキーワード: tubulin, pelophen, peloruside, laulimalide, cell cycle/inhibitor, cell cycle-inhibitor complex
• 由来する生物種: Rattus norvegicus (Norway rat); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 271078.05

構造登録者

Estevez-Gallego, J.,Diaz, J.F.,Van der Eycken, J.,Oliva, M.A. (登録日: 2022-05-20, 公開日: 2022-11-23, 最終更新日: 2024-02-07)

主引用文献

Estevez-Gallego, J.,Alvarez-Bernad, B.,Pera, B.,Wullschleger, C.,Raes, O.,Menche, D.,Martinez, J.C.,Lucena-Agell, D.,Prota, A.E.,Bonato, F.,Bargsten, K.,Cornelus, J.,Gimenez-Abian, J.F.,Northcote, P.,Steinmetz, M.O.,Kamimura, S.,Altmann, K.H.,Paterson, I.,Gago, F.,Van der Eycken, J.,Diaz, J.F.,Oliva, M.A.
Chemical modulation of microtubule structure through the laulimalide/peloruside site.
Structure, 31:88-99.e5, 2023

PubMed Abstract: Taxanes are microtubule-stabilizing agents used in the treatment of many solid tumors, but they often involve side effects affecting the peripheral nervous system. It has been proposed that this could be related to structural modifications on the filament upon drug binding. Alternatively, laulimalide and peloruside bind to a different site also inducing stabilization, but they have not been exploited in clinics. Here, we use a combination of the parental natural compounds and derived analogs to unravel the stabilization mechanism through this site. These drugs settle lateral interactions without engaging the M loop, which is part of the key and lock involved in the inter-protofilament contacts. Importantly, these drugs can modulate the angle between protofilaments, producing microtubules of different diameters. Among the compounds studied, we have found some showing low cytotoxicity and able to induce stabilization without compromising microtubule native structure. This opens the window of new applications for microtubule-stabilizing agents beyond cancer treatment.

PubMed: 36462501
DOI: 10.1016/j.str.2022.11.006

実験手法

X-RAY DIFFRACTION (2.5 Å)