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Structure of Mycobacterium tuberculosis PknB supports a universal activation mechanism for Ser/Thr protein kinases

Nature Structural & Molecular Biology volume 10, pages 168–174 (2003)Cite this article

Abstract

A family of eukaryotic-like Ser/Thr protein kinases occurs in bacteria, but little is known about the structures and functions of these proteins. Here we characterize PknB, a transmembrane signaling kinase from Mycobacterium tuberculosis. The intracellular PknB kinase domain is active autonomously, and the active enzyme is phosphorylated on residues homologous to regulatory phospho-acceptors in eukaryotic Ser/Thr kinases. The crystal structure of the PknB kinase domain in complex with an ATP analog reveals the active conformation. The predicted fold of the PknB extracellular domain matches the proposed targeting domain of penicillin-binding protein 2x. The structural and chemical similarities of PknB to metazoan homologs support a universal activation mechanism of Ser/Thr protein kinases in prokaryotes and eukaryotes.

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Figure 1: Domain structure of PknB and phosphorylation of the intracellular domain.
Figure 2: Crystal structure of the intracellular domain of PknB in complex with ATP-γ-S.
Figure 3: Similarity of the PknB kinase domain and activated eukaryotic Ser/Thr kinases.
Figure 4: Conserved surface sites in PknB.
Figure 5: Model of full-length PknB.

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Acknowledgements

We thank D.S. King for protein molecular weight measurements, K.F. Medzihradszky for LC/MS/MS measurements, J. Holton and E. Skordalakes for help with structure determination, C.A. Settineri for help with the deconvoluted protein mass spectrum, and L. Gay and M. Good for stimulating discussions. We are indebted to J. Kuriyan for encouragement and for pointing out the importance of the regulatory interaction sites in PknB-I. K. Strenge and S. Shieh provided technical support. We are indebted to T. Terwilliger and the TB Structural Genomics Consortium for support. The work was supported by a grant from the NIH. The Advanced Light Source Beamline 8.3.1 was funded by the NSF, the University of California and Henry Wheeler.

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  1. Tracy A. Young, Benedicte Delagoutte and Arnold M. Falick: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Molecular and Cell Biology, 229 Stanley Hall 3206, University of California, Berkeley, 94720-3206, California, USA

    Tracy A. Young, Benedicte Delagoutte, James A. Endrizzi & Tom Alber

  2. Howard Hughes Medical Institute, 16 Barker Hall 3202, University of California, Berkeley, 94720-3202, California, USA

    Arnold M. Falick

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Correspondence to Tom Alber.

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Young, T., Delagoutte, B., Endrizzi, J. et al. Structure of Mycobacterium tuberculosis PknB supports a universal activation mechanism for Ser/Thr protein kinases. Nat Struct Mol Biol 10, 168–174 (2003). https://doi.org/10.1038/nsb897

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