Association of
            <i>Helicobacter pylori</i>
            Antioxidant Activities with Host Colonization Proficiency

Olczak, Adriana A.; Seyler, Richard W.; Olson, Jonathan W.; Maier, Robert J.

doi:10.1128/iai.71.1.580-583.2003

Cited by 75 publications

(77 citation statements)

References 19 publications

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“…Among these, the most abundant one is AhpC. Several functional studies of H. pylori AhpC have shown that the AhpCdeleted mutants have increased sensitivity to oxygen (15), overexpress neutrophil-activating protein (18), and accelerate inactivation of catalase (25). As a member of 2-Cys peroxiredoxins (17,21,31), AhpC has been shown to be Trx-dependent (17,27,32,33).…”

Section: Discussionmentioning

confidence: 99%

“…However, the electron donor flavoprotein (AhpF) used by most bacteria to reduce AhpC was shown to be inactive for the AhpC of H. pylori (21)(22)(23)(24). In addition, some AhpC-deficient mutant strains have been found to have an increase in the expression of neutrophilactivating protein (NapA) (15,18) or a decrease in the activity of catalase (25). Our previous study has also revealed that the transcription and expression of AhpC in H. pylori isolated from duodenal ulcer patients decrease under long-term oxidative stress (Ͼ8 h in 20% O 2 ) (26).…”

mentioning

confidence: 99%

“…AhpC, a member of the thiol-dependent 2-Cys peroxiredoxin family (17), is the most abundant antioxidant protein in H. pylori (18). Previous reports on bacterial AhpC indicated that the protein forms homodimers through an intersubunit disulfide linkage which can then be reduced by electron donors, as exemplified by AhpF in Salmonella typhimurium and AhpD in Mycobacterium tuberculosis (19,20).…”

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confidence: 99%

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

Chuang

Wu²,

Lo³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

132

105

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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 lowmolecular-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.peroxiredoxin ͉ oxidative stress ͉ phylogenetic comparison ͉ dual functionality ͉ quaternary structural change

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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

Chuang

Wu²,

Lo³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

132

105

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“…NapA, a ferritin-like iron-binding protein, is involved in oxidative stress resistance probably through sequestering free iron in the cells (13,14); also, a NADPH quinone reductase (MdaB) confers oxidative stress resistance by maintaining the quinone pool of the cell in the reduced state (15). The disruption of each individual gene for superoxide dismutase, KatA, AhpC, or MdaB affects severely the ability of the bacterium to colonize the host stomach (15)(16)(17)(18), demonstrating the importance of these enzymes in oxidative stress resistance and host colonization.…”

mentioning

confidence: 99%

Role of a Bacterial Organic Hydroperoxide Detoxification System in Preventing Catalase Inactivation

Wang¹,

Conover

Benoit³

et al. 2004

Journal of Biological Chemistry

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In the gastric pathogen Helicobacter pylori, catalase (KatA) and alkyl hydroperoxide reductase (AhpC) are two highly abundant enzymes that are crucial for oxidative stress resistance and survival of the bacterium in the host. Here we report a connection unidentified previously between the two stress resistance enzymes. We observed that the catalase in ahpC mutant cells in comparison with the parent strain is inactivated partially (approximately 50%). The decrease of catalase activity is well correlated with the perturbation of the heme environment in catalase, as detected by electron paramagnetic resonance spectroscopy. To understand the reason for this catalase inactivation, we examined the inhibitory effects of hydroperoxides on H. pylori catalase (either present in cell extracts or added to the purified enzyme) by monitoring the enzyme activity and the EPR signal of catalase. H. pylori catalase is highly resistant to its own substrate, without the loss of enzyme activity by treatment with a molar ratio of 1:3000 H 2 O 2 . However, it is inactivated by lower concentrations of organic hydroperoxides (the substrate of AhpC). Treatment with a molar ratio of 1:400 t-butyl hydroperoxide resulted in an inactivation of catalase by approximately 50%. UV-visible absorption spectra indicated that the catalase inactivation by organic hydroperoxides is caused by the formation of a catalytically incompetent compound II species. To further support the idea that organic hydroperoxides, which accumulate in the ahpC mutant cells, are responsible for the inactivation of catalase, we compared the level of lipid peroxidation found in ahpC mutant cells with that found in wild type cells. The results showed that the total amount of extractable lipid hydroperoxides in the ahpC mutant cells is approximately three times that in the wild type cells. Our findings reveal a novel role of the organic hydroperoxide detoxification system in preventing catalase inactivation.

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“…Based on the number of cysteine residue, they are broadly divided into three subfamilies: the typical 2-Cys Prxs, the atypical 2-Cys Prxs and the 1-Cys Prxs [1]. The common function of this ubiquitous and diverse group of enzymes is their ability to reduce a variety of peroxides to their respective alcohols [2,3]. The majority of the determined peroxiredoxine structures belongs to 2-Cys Prxs family, which has received much attention recently [4].…”

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confidence: 99%

Identification and structure of a novel archaeal HypB for [NiFe] hydrogenase maturation

et al. 2012

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[NiFe] hydrogenase catalyzes the reversible oxidation of molecular hydrogen. The large subunit of the enzyme carries a NiFe(CN) 2 (CO) cluster at the active site. The biosynthesis of the NiFe cluster needs maturation proteins, HypA, HypB, HypC, HypD, HypE, and HypF. After incoorporation of the Fe(CN) 2 CO group, HypB inserts the Ni atom together with HypA. Previously charactrized HypB protein belongs to the G3E family GTPase and GTP hydrolysis is required for the Ni insertion process and maturation. A gene encoding the G3E family HypB is not found in genome of some archaea. On the other hand, a gene showing high sequence similarity to the Mrp/MinD family ATPase is conserved adjacent to the hypA gene on their genome, assuming that this gene encodes a functional homologue of HypB. Here, we identify TK2007 gene product from hyperthermophilic archaeon Thermococcus kodakarensis KOD1 as HypB and determine its crystal structure. A severe growth defect of the ÄTK2007 strain under hydrogenase-required condition was observed and restored by addition of Ni ions, providing convincing evidence that the TK2007 gene product is a novel Mrp/MinD family HypB protein in T. kodakarensis (Tk-mmHypB). The structure of Tk-mmHypB was solved as homodimer related by a non-crystallographic 2-fold axis. Each monomer consists of a central seven-stranded parallel b-sheet surrounded by a-helices. Intriguingly, ADP molecules from E. coli expression system are tightly bound to the protein although we did not attempted to co-crystallize the purified sample with an ATP, suggesting that Tk-mmHypB shows high affinity with an ADP molecule. Significant structural differences between monomers indicate that the C-terminal loop-helix-loop region is related to the affinity for the ADP. Furthermore, the structure around the dimer interface reveals that the dimer formation is required for ATP hydrolysis.Comparison of the nucleotide-binding site with that of the Mrp/MinD family nitrogenase iron NifH protein suggests structural change during the hydrolysis. These structural insights imply the Ni insertion mechanism depending on nucleotide-exchange factor. Our studies on Tk-mmHypB shed new light on structural and functional diversity of HypB proteins in the Ni insertion process in the [NiFe] hydrogenase maturation.

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Association of Helicobacter pylori Antioxidant Activities with Host Colonization Proficiency

Cited by 75 publications

References 19 publications

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

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

Role of a Bacterial Organic Hydroperoxide Detoxification System in Preventing Catalase Inactivation

Identification and structure of a novel archaeal HypB for [NiFe] hydrogenase maturation

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