論文 - 詳細
| RRC ID | 35569 |
|---|---|
| 著者 | Patil AG, Sang PB, Govindan A, Varshney U. |
| タイトル | Mycobacterium tuberculosis MutT1 (Rv2985) and ADPRase (Rv1700) proteins constitute a two-stage mechanism of 8-oxo-dGTP and 8-oxo-GTP detoxification and adenosine to cytidine mutation avoidance. |
| ジャーナル | J Biol Chem |
| Abstract |
Approximately one third of the world population is infected with Mycobacterium tuberculosis, the causative agent of tuberculosis. A better understanding of the pathogen biology is crucial to develop new tools/strategies to tackle its spread and treatment. In the host macrophages, the pathogen is exposed to reactive oxygen species, known to damage dGTP and GTP to 8-oxo-dGTP and 8-oxo-GTP, respectively. Incorporation of the damaged nucleotides in nucleic acids is detrimental to organisms. MutT proteins, belonging to a class of Nudix hydrolases, hydrolyze 8-oxo-G nucleoside triphosphates/diphosphates to the corresponding nucleoside monophosphates and sanitize the nucleotide pool. Mycobacteria possess several MutT proteins. However, a functional homolog of Escherichia coli MutT has not been identified. Here, we characterized MtuMutT1 and Rv1700 proteins of M. tuberculosis. Unlike other MutT proteins, MtuMutT1 converts 8-oxo-dGTP to 8-oxo-dGDP, and 8-oxo-GTP to 8-oxo-GDP. Rv1700 then converts them to the corresponding nucleoside monophosphates. This observation suggests the presence of a two-stage mechanism of 8-oxo-dGTP/8-oxo-GTP detoxification in mycobacteria. MtuMutT1 converts 8-oxo-dGTP to 8-oxo-dGDP with a Km of ∼50 μM and Vmax of ∼0.9 pmol/min per ng of protein, and Rv1700 converts 8-oxo-dGDP to 8-oxo-dGMP with a Km of ∼9.5 μM and Vmax of ∼0.04 pmol/min per ng of protein. Together, MtuMutT1 and Rv1700 offer maximal rescue to E. coli for its MutT deficiency by decreasing A to C mutations (a hallmark of MutT deficiency). We suggest that the concerted action of MtuMutT1 and Rv1700 plays a crucial role in survival of bacteria against oxidative stress. |
| 巻・号 | 288(16) |
| ページ | 11252-62 |
| 公開日 | 2013-4-19 |
| DOI | 10.1074/jbc.M112.442566 |
| PII | S0021-9258(20)67202-7 |
| PMID | 23463507 |
| PMC | PMC3630869 |
| MeSH | 8-Hydroxy-2'-Deoxyguanosine Adenosine / genetics Adenosine / metabolism* Bacterial Proteins / genetics Bacterial Proteins / metabolism* Cytidine / genetics Cytidine / metabolism* Deoxyguanosine / analogs & derivatives* Deoxyguanosine / genetics Deoxyguanosine / metabolism Humans Mutation Mycobacterium tuberculosis / enzymology* Mycobacterium tuberculosis / genetics Oxidative Stress / physiology* Pyrophosphatases / genetics Pyrophosphatases / metabolism* Sequence Homology, Amino Acid |
| IF | 4.238 |
| 引用数 | 20 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 原核生物(大腸菌) | JW0097-KC |