title: Helicobacter pylori CagA inhibits PAR1-MARK family kinases by mimicking host substrates.
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.
authors: Laboratory of Structural Microbiology, Rockefeller University, New York, New York, USA.
authors: Dragana
authors: D
authors: Nesić
authors: Marshall C
authors: MC
authors: Miller
authors: Zachary T
authors: ZT
authors: Quinkert
authors: Markus
authors: M
authors: Stein
authors: Brian T
authors: BT
authors: Chait
authors: C Erec
authors: CE
authors: Stebbins
mesh_terms: D000942:Antigens, Bacterial / Q000737:chemistry / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D002850:Chromatography, Gel; D016480:Helicobacter pylori / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D016296:Mutagenesis; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C080866:cagA protein, Helicobacter pylori; C094670:MARK2 protein, human; D017346:Protein Serine-Threonine Kinases