Biochemistry

Uninhibited Mimicry

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Science  22 Jan 2010:
Vol. 327, Issue 5964, pp. 395
DOI: 10.1126/science.327.5964.395-b
CREDIT: NÊSIĆ ET AL., NAT. STRUCT. MOL. BIOL. 17, 130 (2010)

Helicobacter pylori is a pathogen that causes gastric disease and is associated epidemiologically with gastric cancer. This bacterium injects its protein CagA into epithelial cells lining the stomach in order to disrupt cellular functions, and a domain of CagA that contains contiguous repeats acts to inhibit the PAR1-MARK family of protein serine-threonine kinases.

Neŝić et al. describe the 2.2 Å crystal structure of the human kinase MARK2 in complex with a 120-residue repeat-containing subdomain of CagA. Unusually, the kinase adopts an active conformation even though there is no magnesium or ATP present, and a 14-residue CagA segment was observed to occupy the MARK2 substrate-binding site. This peptide appeared to promote and stabilize the active conformation of MARK2 by mimicking conserved features of the host substrates of this protein kinase family in a fashion reminiscent of the inhibition of the cAMP-dependent protein kinase by the endogenous peptide PKI.

Nat. Struct. Mol. Biol. 17, 130 (2010).

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