2FUM

Catalytic domain of protein kinase PknB from Mycobacterium tuberculosis in complex with mitoxantrone

Summary for 2FUM

• Entry DOI: 10.2210/pdb2fum/pdb
• Related: 1O6Y
• Descriptor: Probable serine/threonine-protein kinase pknB, 1,4-DIHYDROXY-5,8-BIS({2-[(2-HYDROXYETHYL)AMINO]ETHYL}AMINO)-9,10-ANTHRACENEDIONE (2 entities in total)
• Functional Keywords: protein kinase-inhibitor complex, transferase
• Biological source: Mycobacterium tuberculosis H37Rv
• Total number of polymer chains: 4
• Total formula weight: 131611.95

Authors

Wehenkel, A.,Alzari, P.M. (deposition date: 2006-01-27, release date: 2006-08-01, Last modification date: 2023-10-25)

Primary citation

Wehenkel, A.,Fernandez, P.,Bellinzoni, M.,Catherinot, V.,Barilone, N.,Labesse, G.,Jackson, M.,Alzari, P.M.
The structure of PknB in complex with mitoxantrone, an ATP-competitive inhibitor, suggests a mode of protein kinase regulation in mycobacteria
Febs Lett., 580:3018-3022, 2006

PubMed 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.

PubMed: 16674948
DOI: 10.1016/j.febslet.2006.04.046

Experimental method

X-RAY DIFFRACTION (2.89 Å)