title: The structure of PknB in complex with mitoxantrone, an ATP-competitive inhibitor, suggests a mode of protein kinase regulation in mycobacteria.
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.
authors: Unité de Biochimie Structurale and CNRS URA2185, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris, France.
authors: Annemarie
authors: A
authors: Wehenkel
authors: Pablo
authors: P
authors: Fernandez
authors: Marco
authors: M
authors: Bellinzoni
authors: Vincent
authors: V
authors: Catherinot
authors: Nathalie
authors: N
authors: Barilone
authors: Gilles
authors: G
authors: Labesse
authors: Mary
authors: M
authors: Jackson
authors: Pedro M
authors: PM
authors: Alzari