Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2052580 | FEBS Letters | 2006 | 5 Pages |
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.
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Authors
Annemarie Wehenkel, Pablo Fernandez, Marco Bellinzoni, Vincent Catherinot, Nathalie Barilone, Gilles Labesse, Mary Jackson, Pedro M. Alzari,