Exploring Critical Components for MutS Activity in Helicobacter pylori

描述(由申请人提供)：幽门螺杆菌是一种人类胃部病原体，它在胃粘膜中的持久性部分归因于它能抵抗宿主的防御。细菌修复其氧化的大分子的显著能力，包括其DNA，是促进幽门螺杆菌生存的因素之一。幽门螺杆菌MutS蛋白似乎在DNA识别、修复和重组中发挥着多种独特的作用。然而，这些酶的不同功能背后的分子机制还不清楚，也没有确定其相互作用的伙伴蛋白。这里的目标是通过酶分析、定点突变和蛋白质-蛋白质相互作用的方法，在分子水平上开始了解MutS修复功能。与公共卫生相关：该项目涉及对一种流行的人类病原体用来使其在人类体内存活的因素进行表征。长期目标是能够挫败细菌抵抗宿主建立的防御机制的能力。

DESCRIPTION (provided by applicant): Helicobacter pylori is a gastric pathogen of humans, and its persistence in the gastric mucosa has been in part attributed to its ability to counteract the host defense. The bacterium's marked ability to repair its oxidized macromolecules, including its DNA is one factor facilitating Helicobacter survival. The H. pylori MutS protein appears to play multiple and unique roles in DNA recognition, repair, and in recombination. However, the molecular mechanisms underlying the enzymes diverse functions are not understood, nor have its interacting partner proteins been identified. The goal here is to begin to understand the MutS repair function on a molecular level via enzyme assays, site-specific mutagenesis, and protein-protein interaction approaches. PUBLIC HEALTH RELEVANCE: The project involves characterization of factors used by a prevalent human pathogen to enable its survival in humans. The long term goal is to be able to thwart the ability of the bacterium to resist the defense mechanisms mounted by the host.