2FUM

Catalytic domain of protein kinase PknB from Mycobacterium tuberculosis in complex with mitoxantrone

2FUM の概要

• エントリーDOI: 10.2210/pdb2fum/pdb
• 関連するPDBエントリー: 1O6Y
• 分子名称: Probable serine/threonine-protein kinase pknB, 1,4-DIHYDROXY-5,8-BIS({2-[(2-HYDROXYETHYL)AMINO]ETHYL}AMINO)-9,10-ANTHRACENEDIONE (2 entities in total)
• 機能のキーワード: protein kinase-inhibitor complex, transferase
• 由来する生物種: Mycobacterium tuberculosis H37Rv
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 131611.95

構造登録者

Wehenkel, A.,Alzari, P.M. (登録日: 2006-01-27, 公開日: 2006-08-01, 最終更新日: 2023-10-25)

主引用文献

Wehenkel, A.,Fernandez, P.,Bellinzoni, M.,Catherinot, V.,Barilone, N.,Labesse, G.,Jackson, M.,Alzari, P.M.
The structure of PknB in complex with mitoxantrone, an ATP-competitive inhibitor, suggests a mode of protein kinase regulation in mycobacteria
Febs Lett., 580:3018-3022, 2006

PubMed Abstract: Mycobacterium tuberculosis PknB is an essential receptor-like protein kinase involved in cell growth control. Here, we demonstrate that mitoxantrone, an anthraquinone derivative used in cancer therapy, is a PknB inhibitor capable of preventing mycobacterial growth. The structure of the complex reveals that mitoxantrone partially occupies the adenine-binding pocket in PknB, providing a framework for the design of compounds with potential therapeutic applications. PknB crystallizes as a 'back-to-back' homodimer identical to those observed in other structures of PknB in complex with ATP analogs. This organization resembles that of the RNA-dependent protein kinase PKR, suggesting a mechanism for kinase activation in mycobacteria.

PubMed: 16674948
DOI: 10.1016/j.febslet.2006.04.046

実験手法

X-RAY DIFFRACTION (2.89 Å)