H PYLORI CAGA INHIBITS PAR1-MARK FAMILY KINASES BY MIMICKING HOST SUBSTRATES

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 幽门螺杆菌的CagA蛋白与许多细胞因子相互作用，并与胃癌的毒力和风险增加有关。我们在这里提出的CagA与人类激酶PAR 1b/MARK 2的一个亚结构域的共晶结构，揭示了CagA肽模拟底物的激酶家族，类似真核蛋白激酶抑制剂。对这种相互作用起中心作用的保守残基的突变使得CagA作为MARK 2的抑制剂失活

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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