The structure of PknB in complex with mitoxantrone, an ATP-competitive inhibitor, suggests a mode of protein kinase regulation in mycobacteria. - Archive ouverte HAL Access content directly
Journal Articles FEBS Letters Year : 2006

The structure of PknB in complex with mitoxantrone, an ATP-competitive inhibitor, suggests a mode of protein kinase regulation in mycobacteria.

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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.

Dates and versions

pasteur-03144516 , version 1 (17-02-2021)

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Annemarie Wehenkel, Pablo Fernandez, Marco Bellinzoni, Vincent Catherinot, Nathalie Barilone, et al.. The structure of PknB in complex with mitoxantrone, an ATP-competitive inhibitor, suggests a mode of protein kinase regulation in mycobacteria.. FEBS Letters, 2006, 580 (13), pp.3018-22. ⟨10.1016/j.febslet.2006.04.046⟩. ⟨pasteur-03144516⟩
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