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The antioxidant protein alkylhydroperoxide reductase of Helicobacter pylori switches from a peroxide reductase to a molecular chaperone function.

ABSTRACT: Helicobacter pylori, an oxygen-sensitive microaerophilic bacterium, contains many antioxidant proteins, among which alkylhydroperoxide reductase (AhpC) is the most abundant. The function of AhpC is to protect H. pylori from a hyperoxidative environment by reduction of toxic organic hydroperoxides. We have found that the sequence of AhpC from H. pylori is more homologous to mammalian peroxiredoxins than to eubacterial AhpC. We have also found that the protein structure of AhpC could shift from low-molecular-weight oligomers with peroxide-reductase activity to high-molecular-weight complexes with molecular-chaperone function under oxidative stresses. Time-course study by following the quaternary structural change of AhpC in vivo revealed that this enzyme changes from low-molecular-weight oligomers under normal microaerobic conditions or short-term oxidative shock to high-molecular-weight complexes after severe long-term oxidative stress. This study revealed that AhpC of H. pylori acts as a peroxide reductase in reducing organic hydroperoxides and as a molecular chaperone for prevention of protein misfolding under oxidative stress.

SUBMITTER: Chuang MH

PROVIDER: S-EPMC1413804 | biostudies-literature | 2006 Feb

REPOSITORIES: biostudies-literature

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The antioxidant protein alkylhydroperoxide reductase of Helicobacter pylori switches from a peroxide reductase to a molecular chaperone function.

Chuang Ming-Hong MH Wu Ming-Shiang MS Lo Wan-Lin WL Lin Jaw-Town JT Wong Chi-Huey CH Chiou Shyh-Horng SH

Proceedings of the National Academy of Sciences of the United States of America 20060215 8

Helicobacter pylori, an oxygen-sensitive microaerophilic bacterium, contains many antioxidant proteins, among which alkylhydroperoxide reductase (AhpC) is the most abundant. The function of AhpC is to protect H. pylori from a hyperoxidative environment by reduction of toxic organic hydroperoxides. We have found that the sequence of AhpC from H. pylori is more homologous to mammalian peroxiredoxins than to eubacterial AhpC. We have also found that the protein structure of AhpC could shift from lo ...[more]

PMID: 16481626

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Project description:The well-studied catalytic role of urease, the Ni-dependent conversion of urea into carbon dioxide and ammonia, has been shown to protect Helicobacter pylori against the low pH environment of the stomach lumen. We hypothesized that the abundantly expressed urease protein can play another noncatalytic role in combating oxidative stress via Met residue-mediated quenching of harmful oxidants. Three catalytically inactive urease mutant strains were constructed by single substitutions of Ni binding residues. The mutant versions synthesize normal levels of urease, and the altered versions retained all methionine residues. The three site-directed urease mutants were able to better withstand a hypochlorous acid (HOCl) challenge than a ?ureAB deletion strain. The capacity of purified urease to protect whole cells via oxidant quenching was assessed by adding urease enzyme to nongrowing HOCl-exposed cells. No wild-type cells were recovered with oxidant alone, whereas urease addition significantly aided viability. These results suggest that urease can protect H. pylori against oxidative damage and that the protective ability is distinct from the well-characterized catalytic role. To determine the capability of methionine sulfoxide reductase (Msr) to reduce oxidized Met residues in urease, purified H. pylori urease was exposed to HOCl and a previously described Msr peptide repair mixture was added. Of the 25 methionine residues in urease, 11 were subject to both oxidation and to Msr-mediated repair, as identified by mass spectrometry (MS) analysis; therefore, the oxidant-quenchable Met pool comprising urease can be recycled by the Msr repair system. Noncatalytic urease appears to play an important role in oxidant protection.IMPORTANCE Chronic Helicobacter pylori infection can lead to gastric ulcers and gastric cancers. The enzyme urease contributes to the survival of the bacterium in the harsh environment of the stomach by increasing the local pH. In addition to combating acid, H. pylori must survive host-produced reactive oxygen species to persist in the gastric mucosa. We describe a cyclic amino acid-based antioxidant role of urease, whereby oxidized methionine residues can be recycled by methionine sulfoxide reductase to again quench oxidants. This work expands our understanding of the role of an already acknowledged pathogen virulence factor and specifically expands our knowledge of H. pylori survival mechanisms.

Dataset Information

The antioxidant protein alkylhydroperoxide reductase of Helicobacter pylori switches from a peroxide reductase to a molecular chaperone function.

Publications

The antioxidant protein alkylhydroperoxide reductase of Helicobacter pylori switches from a peroxide reductase to a molecular chaperone function.

Similar Datasets

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