6GF3

Tubulin-Jerantinine B acetate complex

6GF3 の概要

• エントリーDOI: 10.2210/pdb6gf3/pdb
• 分子名称: Tubulin alpha-1B chain, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, Jerantinine B, ... (14 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 (Norway Rat); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 265125.67

構造登録者

Smedley, C.J.,Stanley, P.A.,Qazzaz, M.E.,Prota, A.E.,Olieric, N.,Collins, H.,Eastman, H.,Barrow, A.S.,Lim, K.-H.,Kam, T.-S.,Smith, B.J.,Duivenvoorden, H.M.,Parker, B.S.,Bradshaw, T.D.,Steinmetz, M.O.,Moses, J.E. (登録日: 2018-04-29, 公開日: 2019-05-08, 最終更新日: 2024-01-17)

主引用文献

Smedley, C.J.,Stanley, P.A.,Qazzaz, M.E.,Prota, A.E.,Olieric, N.,Collins, H.,Eastman, H.,Barrow, A.S.,Lim, K.H.,Kam, T.S.,Smith, B.J.,Duivenvoorden, H.M.,Parker, B.S.,Bradshaw, T.D.,Steinmetz, M.O.,Moses, J.E.
Sustainable Syntheses of (-)-Jerantinines A & E and Structural Characterisation of the Jerantinine-Tubulin Complex at the Colchicine Binding Site.
Sci Rep, 8:10617-10617, 2018

PubMed Abstract: The jerantinine family of Aspidosperma indole alkaloids from Tabernaemontana corymbosa are potent microtubule-targeting agents with broad spectrum anticancer activity. The natural supply of these precious metabolites has been significantly disrupted due to the inclusion of T. corymbosa on the endangered list of threatened species by the International Union for Conservation of Nature. This report describes the asymmetric syntheses of (-)-jerantinines A and E from sustainably sourced (-)-tabersonine, using a straight-forward and robust biomimetic approach. Biological investigations of synthetic (-)-jerantinine A, along with molecular modelling and X-ray crystallography studies of the tubulin-(-)-jerantinine B acetate complex, advocate an anticancer mode of action of the jerantinines operating via microtubule disruption resulting from binding at the colchicine site. This work lays the foundation for accessing useful quantities of enantiomerically pure jerantinine alkaloids for future development.

PubMed: 30006510
DOI: 10.1038/s41598-018-28880-2

実験手法

X-RAY DIFFRACTION (2.4 Å)