Amino Acid Repair Activity in Helicobacter pylori

描述(由申请人提供)：蛋氨酸亚麻酸还原酶(MSR‘s)催化甲硫氨酸亚砜还原为(正常)蛋氨酸。其结果是氧化损伤的蛋白质重新激活，这种活性被认为有助于幽门螺杆菌成功地在胃中定植。该项目旨在确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。将识别两种类型的功能残基。这些是MSR修复的特异性Met残基，以及参与识别MSR的残基。关键的残基类型将通过研究纯的幽门螺杆菌MSR及其与已鉴定的靶蛋白的相互作用来确定。来自纯蛋白研究的信息将被用来评估整个细胞暴露应激剂时目标蛋白中Met残基氧化损伤的程度。然后，将利用单个靶蛋白对接位点(MSR相互作用位点)的信息来了解幽门螺杆菌应激生理和胃定植能力中每个靶蛋白修复的必要性。公共卫生相关性：持续的人类病原体幽门螺杆菌对蛋氨酸的修复对该细菌在胃中的生存非常重要。用于修复富含蛋氨酸的蛋白质的机制以及这种修复的生理后果将被揭示，从而可以开发出对抗病原体的措施。

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.