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- Publisher Website: 10.1007/s00775-017-1452-5
- Scopus: eid_2-s2.0-85016626056
- WOS: WOS:000405434700005
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Article: Functional disruption of peroxiredoxin by bismuth antiulcer drugs attenuates Helicobacter pylori survival
Title | Functional disruption of peroxiredoxin by bismuth antiulcer drugs attenuates <i>Helicobacter pylori</i> survival |
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Authors | |
Keywords | Bismuth drug Enzyme Molecular mechanism Oxidative stress Peroxiredoxin |
Issue Date | 2017 |
Citation | Journal of Biological Inorganic Chemistry, 2017, v. 22, p. 673-683 How to Cite? |
Abstract | Bismuth drugs have been used clinically to treat infections from Helicobacter pylori, a pathogen that is strongly related to gastrointestinal diseases even stomach cancer. Despite extensive studies, the mechanisms of action of bismuth drugs are not fully understood. Alkyl hydroperoxide reductase subunit C (AhpC) is the most abundant 2-cysteine peroxiredoxin, crucial for H. pylori survival in the host by defense of oxidative stress. Herein we show that a Bi(III) antiulcer drug (CBS) binds to the highly conserved cysteine residues (Cys49 and Cys169) with a dissociation constant (K d) of Bi(III) to AhpC of 3.0 (±1.0) × 10−24 M. Significantly the interaction of CBS with AhpC disrupts the peroxiredoxin and chaperone activities of the enzyme both in vitro and in bacterial cells, leading to attenuated bacterial survival. Moreover, using a home-made fluorescent probe, we demonstrate that Bi(III) also perturbs AhpC relocation between the cytoplasm and membrane region in decomposing the exogenous ROS. Our study suggests that disruption of redox homeostasis by bismuth drugs via interaction with key enzymes such as AhpC contributes to their antimicrobial activity. |
Persistent Identifier | http://hdl.handle.net/10722/244792 |
ISSN | 2023 Impact Factor: 2.7 2023 SCImago Journal Rankings: 0.543 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Chang, YY | - |
dc.contributor.author | Cheng, T | - |
dc.contributor.author | Yang, X | - |
dc.contributor.author | Jin, L | - |
dc.contributor.author | Sun, H | - |
dc.contributor.author | Li, H | - |
dc.date.accessioned | 2017-09-18T01:59:09Z | - |
dc.date.available | 2017-09-18T01:59:09Z | - |
dc.date.issued | 2017 | - |
dc.identifier.citation | Journal of Biological Inorganic Chemistry, 2017, v. 22, p. 673-683 | - |
dc.identifier.issn | 0949-8257 | - |
dc.identifier.uri | http://hdl.handle.net/10722/244792 | - |
dc.description.abstract | Bismuth drugs have been used clinically to treat infections from Helicobacter pylori, a pathogen that is strongly related to gastrointestinal diseases even stomach cancer. Despite extensive studies, the mechanisms of action of bismuth drugs are not fully understood. Alkyl hydroperoxide reductase subunit C (AhpC) is the most abundant 2-cysteine peroxiredoxin, crucial for H. pylori survival in the host by defense of oxidative stress. Herein we show that a Bi(III) antiulcer drug (CBS) binds to the highly conserved cysteine residues (Cys49 and Cys169) with a dissociation constant (K d) of Bi(III) to AhpC of 3.0 (±1.0) × 10−24 M. Significantly the interaction of CBS with AhpC disrupts the peroxiredoxin and chaperone activities of the enzyme both in vitro and in bacterial cells, leading to attenuated bacterial survival. Moreover, using a home-made fluorescent probe, we demonstrate that Bi(III) also perturbs AhpC relocation between the cytoplasm and membrane region in decomposing the exogenous ROS. Our study suggests that disruption of redox homeostasis by bismuth drugs via interaction with key enzymes such as AhpC contributes to their antimicrobial activity. | - |
dc.language | eng | - |
dc.relation.ispartof | Journal of Biological Inorganic Chemistry | - |
dc.subject | Bismuth drug | - |
dc.subject | Enzyme | - |
dc.subject | Molecular mechanism | - |
dc.subject | Oxidative stress | - |
dc.subject | Peroxiredoxin | - |
dc.title | Functional disruption of peroxiredoxin by bismuth antiulcer drugs attenuates <i>Helicobacter pylori</i> survival | - |
dc.type | Article | - |
dc.identifier.email | Cheng, T: chengtfc@hku.hk | - |
dc.identifier.email | Yang, X: xmy2014@hku.hk | - |
dc.identifier.email | Jin, L: ljjin@hkucc.hku.hk | - |
dc.identifier.email | Sun, H: hsun@hku.hk | - |
dc.identifier.email | Li, H: hylichem@hku.hk | - |
dc.identifier.authority | Jin, L=rp00028 | - |
dc.identifier.authority | Sun, H=rp00777 | - |
dc.identifier.doi | 10.1007/s00775-017-1452-5 | - |
dc.identifier.scopus | eid_2-s2.0-85016626056 | - |
dc.identifier.hkuros | 278092 | - |
dc.identifier.volume | 22 | - |
dc.identifier.spage | 673 | - |
dc.identifier.epage | 683 | - |
dc.identifier.eissn | 1432-1327 | - |
dc.identifier.isi | WOS:000405434700005 | - |
dc.identifier.issnl | 0949-8257 | - |