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pubmed-article:16674948pubmed:abstractTextMycobacterium 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.lld:pubmed
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pubmed-article:16674948pubmed:dateRevised2007-11-15lld:pubmed
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pubmed-article:16674948pubmed:articleTitleThe structure of PknB in complex with mitoxantrone, an ATP-competitive inhibitor, suggests a mode of protein kinase regulation in mycobacteria.lld:pubmed
pubmed-article:16674948pubmed:affiliationUnité de Biochimie Structurale and CNRS URA2185, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris, France.lld:pubmed
pubmed-article:16674948pubmed:publicationTypeJournal Articlelld:pubmed
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