4O4L

Tubulin-Peloruside A-Epothilone A complex

4O4L の概要

• エントリーDOI: 10.2210/pdb4o4l/pdb
• 関連するPDBエントリー: 4O4H 4O4I 4O4J
• 分子名称: Tubulin alpha-1B chain, EPOTHILONE A, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, ... (12 entities in total)
• 機能のキーワード: alpha-tubulin, beta-tubulin, ligase, gtpase, microtubule, stathmin, peloruside a, epothilone a, tubulin fold, cytoskeleton, cell cycle-inhibitor complex, cell cycle/inhibitor
• 由来する生物種: Rattus norvegicus (rat); 詳細
• 細胞内の位置: Cytoplasm, cytoskeleton: P81947; Cytoplasm, cytoskeleton (By similarity): Q6B856; Golgi apparatus: P63043
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 266061.41

構造登録者

Prota, A.E.,Bargsten, K.,Northcote, P.T.,Marsh, M.,Altmann, K.H.,Miller, J.H.,Diaz, J.F.,Steinmetz, M.O. (登録日: 2013-12-18, 公開日: 2014-03-26, 最終更新日: 2024-04-03)

主引用文献

Prota, A.E.,Bargsten, K.,Northcote, P.T.,Marsh, M.,Altmann, K.H.,Miller, J.H.,Diaz, J.F.,Steinmetz, M.O.
Structural basis of microtubule stabilization by laulimalide and peloruside a.
Angew.Chem.Int.Ed.Engl., 53:1621-1625, 2014

PubMed Abstract: Laulimalide and peloruside A are microtubule-stabilizing agents (MSAs), the mechanism of action on microtubules of which is poorly defined. Here, using X-ray crystallography it is shown that laulimalide and peloruside A bind to a unique non-taxane site on β-tubulin and use their respective macrolide core structures to interact with a second tubulin dimer across protofilaments. At the same time, they allosterically stabilize the taxane-site M-loop that establishes lateral tubulin contacts in microtubules. Structures of ternary complexes of tubulin with laulimalide/peloruside A and epothilone A are also solved, and a crosstalk between the laulimalide/peloruside and taxane sites via the M-loop of β-tubulin is found. Together, the data define the mechanism of action of laulimalide and peloruside A on tubulin and microtubules. The data further provide a structural framework for understanding the synergy observed between two classes of MSAs in tubulin assembly and the inhibition of cancer cell growth.

PubMed: 24470331
DOI: 10.1002/anie.201307749

実験手法

X-RAY DIFFRACTION (2.2 Å)