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.
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.
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