Amino Acid Repair Activity in Helicobacter pylori

描述（由申请人提供）：蛋氨酸亚砜还原酶（Msr's）催化蛋氨酸亚砜还原为（正常）蛋氨酸。结果是氧化损伤蛋白的再激活，这种活性已知有助于幽门螺杆菌成功定植胃。该项目旨在鉴定与三种已鉴定的幽门螺杆菌蛋白相关的关键氨基酸残基，这些蛋白经历了这种还原修复过程。将鉴定两种类型的功能残基。这些是被Msr修复的特异的Met残基，以及参与识别Msr的残基。通过研究纯幽门螺杆菌Msr及其与已鉴定的靶蛋白的相互作用，将确定关键的残基类型。来自纯蛋白质研究的信息将用于评估应激剂暴露于全细胞时靶蛋白的氧化Met残基损伤程度。然后利用单个靶蛋白对接位点（msr相互作用位点）的信息来了解每个靶蛋白在幽门螺杆菌应激生理和胃定殖能力中的修复需求。公共卫生相关性：持续存在的人类病原体幽门螺杆菌对蛋氨酸的修复对于细菌在胃中存活是重要的。用于修复富含蛋氨酸的蛋白质的机制和这种修复的生理后果将被揭示，以便可以开发对抗病原体的措施。

DESCRIPTION (provided by applicant): Methionine sulfoxide reductases (Msr's) catalyze the reduction of methionine sulfoxide back to (normal) methionine. The result is reactivation of oxidatively damaged proteins and this activity is known to facilitate successful gastric colonization by H. pylori. This project is designed to identify the critical amino acid residues associated with three identified H. pylori proteins that undergo this reductive repair process. Two types of functional residues will be identified. These are the specific Met residues repaired by Msr, and the residues involved in recognizing Msr. The key types of residues will be identified by studying pure H. pylori Msr and its interaction with identified target proteins. The information from the pure protein studies will be used to assess the degree of oxidative Met residue damage in the target proteins upon stress agent exposure of whole cells. Then the information on the individual target proteins docking sites (Msr-interacting sites) will be used to understand the need for each target proteins repair in H. pylori stress physiology and stomach colonizing abilities. PUBLIC HEALTH RELEVANCE: Methionine repair by the persistent human pathogen Helicobacter pylori is important for the bacterium to survive in the stomach. The mechanisms used to repair methionine-rich proteins and the physiological consequences of such repair will be uncovered so that measures to counteract the pathogen can be developed.