Broad specificity AhpC-like peroxiredoxin and its thioredoxin reductant in the sparse antioxidant defense system of Treponema pallidum
| Autor: | David L. Cox, Karsten R. O. Hazlett, Leslie B. Poole, Derek Parsonage, Kimberly J. Nelson, Yongcheng Sun, Daniel C. Desrosiers, Justin D. Radolf |
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| Rok vydání: | 2010 |
| Předmět: |
Transcription
Genetic Molecular Sequence Data Biology Antioxidants Substrate Specificity chemistry.chemical_compound Thioredoxins Animals Amino Acid Sequence Treponema pallidum Peptide sequence Gene chemistry.chemical_classification Multidisciplinary Treponema Peroxiredoxins Glutathione Biological Sciences biology.organism_classification Enzyme chemistry Biochemistry biology.protein Rabbits Thioredoxin Peroxiredoxin Oxidation-Reduction Sequence Alignment Genome Bacterial Peroxidase |
| Zdroj: | Proceedings of the National Academy of Sciences. 107:6240-6245 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.0910057107 |
| Popis: | Little is known about the mechanisms by which Treponema pallidum ( Tp ), the causative agent of syphilis, copes with oxidative stress as it establishes persistent infection within its obligate human host. The Tp genomic sequence indicates that the bacterium’s antioxidant defenses do not include glutathione and are limited to just a few proteins, with only one, TP0509, offering direct defense against peroxides. Although this Tp peroxiredoxin (Prx) closely resembles AhpC-like Prxs, Tp lacks AhpF, the typical reductant for such enzymes. Functionally, Tp AhpC resembles largely eukaryotic, nonAhpC typical 2-Cys Prx proteins in using thioredoxin (Trx, TP0919) as an efficient electron donor and exhibiting broad specificity toward hydroperoxide substrates. Unlike many of the eukaryotic Prxs, however, Tp AhpC is relatively resistant to inactivation during turnover with hydroperoxide substrates. As is often observed in typical 2-Cys Prxs, Tp AhpC undergoes redox-sensitive oligomer formation. Quantitative immunoblotting revealed that Tp Trx and Tp AhpC are present at very high levels (over 100 and 300 μM, respectively) in treponemes infecting rabbit testes; their redox potentials, at -242 ± 1 and -192 ± 2 mV, respectively, are consistent with the role of Tp Trx as the cellular reductant of Tp AhpC. Transcriptional analysis of select antioxidant genes confirmed the presence of high mRNA levels for ahpC and trx which diminish greatly when spirochetes replicate under in vitro growth conditions. Thus, T. pallidum has evolved an extraordinarily robust, broad-spectrum AhpC as its sole mechanism for peroxide defense to combat this significant threat to treponemal growth and survival during infection. |
| Databáze: | OpenAIRE |
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