Amino Acid Repair Activity in Helicobacter pylori

幽门螺杆菌的氨基酸修复活性

基本信息

批准号：
7994871
负责人：
ROBERT J. MAIER
金额：
$ 36.14万
依托单位：
UNIVERSITY OF GEORGIA
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-12-01 至 2013-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7994871
关键词：
Address Affect Amino Acids Area Back Bacteria Binding Biochemical Cells Characteristics Complement Digestion Docking Ensure Escherichia coli Event Funding Future Glean Goals Grant Health Helicobacter Helicobacter pylori Human In Vitro Individual Inflammation Inflammatory Response Knowledge Light Maps Measures Mediating Methionine Methods Modeling Molecular Monitor Mus Mutation Neisseria Organism Outcome Oxidants Oxidative Stress Parents Pattern Peptides Physiological Physiology Procedures Process Property Proteins Proteome Research Resistance Role Series Site Site-Directed Mutagenesis Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Stomach Stress System Therapeutic Thioredoxin Trypsin United States National Institutes of Health Work base benzyl-(1-amino-3-chloro-2-propanol)catalase crosslink design domain mapping in vivo interest macromolecule meetings methionine sulfoxide methionine sulfoxide reductase mutant oxidation pathogen protein protein interaction recombinase repair enzyme repaired success sulfoxide reductase

项目摘要

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.

描述（由申请人提供）：甲硫氨酸还原酶（MSR）催化甲硫氨酸的硫氨酸还原回（正常）蛋氨酸。结果是氧化受损的蛋白质的重新激活，已知该活性促进幽门螺杆菌成功的胃定植。该项目旨在识别与经历此还原性修复过程的三个已鉴定的幽门螺杆菌蛋白相关的关键氨基酸残基。将确定两种类型的功能残基。这些是MSR修复的特定MET残基，以及识别MSR的残基。通过研究纯H.幽门螺杆菌MSR及其与已鉴定的靶蛋白的相互作用，将确定残基的关键类型。来自纯蛋白质研究的信息将用于评估全细胞应力剂暴露时靶蛋白中氧化的残留损伤程度。然后，将使用有关单个靶蛋白对接位点（MSR相互作用位点）的信息来理解幽门螺杆菌胁迫生理和胃部定植能力中每种靶蛋白修复的需求。公共卫生相关性：持续的人类病原体幽门螺杆菌修复甲硫氨酸对细菌在胃中生存至关重要。将发现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，以便可以开发出来抵消病原体的措施。