%0 Journal Article %T The structure of PknB in complex with mitoxantrone, an ATP-competitive inhibitor, suggests a mode of protein kinase regulation in mycobacteria. %+ Biochimie Structurale %+ Centre de Biochimie Structurale [Montpellier] (CBS) %+ Génétique mycobactérienne - Mycobacterial genetics %A Wehenkel, Annemarie %A Fernandez, Pablo %A Bellinzoni, Marco %A Catherinot, Vincent %A Barilone, Nathalie %A Labesse, Gilles %A Jackson, Mary %A Alzari, Pedro, M. %Z This work has been supported by grants from the Institut Pasteur (GPH‐Tuberculose) and the European Commission (X‐TB, contract QLK2‐CT‐2001‐02018). %< avec comité de lecture %@ 0014-5793 %J FEBS Letters %I Wiley %V 580 %N 13 %P 3018-22 %8 2006-05-29 %D 2006 %R 10.1016/j.febslet.2006.04.046 %M 16674948 %K Drug design %K Back-to-back dimerization %K Crystal structure %K Ser/Thr protein kinase-inhibitor complex %K Mycobacterium tuberculosis %Z Chemical Sciences/Cristallography %Z Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM] %Z Life Sciences [q-bio]/Biochemistry, Molecular Biology %Z Computer Science [cs]/Bioinformatics [q-bio.QM] %Z Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph] %Z Life Sciences [q-bio]/Cellular BiologyJournal articles %X 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. %G English %L pasteur-03144516 %U https://pasteur.hal.science/pasteur-03144516 %~ PASTEUR %~ CNRS %~ CBS %~ BS %~ UNIV-MONTPELLIER %~ UM-2015-2021