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Nat Struct Mol Biol. 2010 Jan;17(1):130-2. doi: 10.1038/nsmb.1705. Epub 2009 Dec 6.

Helicobacter pylori CagA inhibits PAR1-MARK family kinases by mimicking host substrates.

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  • 1Laboratory of Structural Microbiology, Rockefeller University, New York, New York, USA.

Abstract

The CagA protein of Helicobacter pylori interacts with numerous cellular factors and is associated with increased virulence and risk of gastric carcinoma. We present here the cocrystal structure of a subdomain of CagA with the human kinase PAR1b/MARK2, revealing that a CagA peptide mimics substrates of this kinase family, resembling eukaryotic protein kinase inhibitors. Mutagenesis of conserved residues central to this interaction renders CagA inactive as an inhibitor of MARK2.

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