A thermophilic 8-oxoguanine DNA glycosylase from Thermococcus barophiluss Ch5 is a new member of AGOG DNA glycosylase family
<?A3B2 tlsb=-.002w?>8-Oxoguanine (8oxoG) in DNA is a major oxidized base that poses a severe threat to genome stability. To counteract the mutagenic effect generated by 8oxoG in DNA, cells have evolved 8oxoG DNA glycosylase (OGG) that can excise this oxidized base from DNA. Currently, OGG enzy...
| المؤلفون الرئيسيون: | , , |
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| التنسيق: | مقال |
| اللغة: | English |
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China Science Publishing & Media Ltd.
2022-06-01
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| سلاسل: | Acta Biochimica et Biophysica Sinica |
| الموضوعات: | |
| الوصول للمادة أونلاين: | https://www.sciengine.com/doi/10.3724/abbs.2022072 |
| _version_ | 1827769086638030848 |
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| author | Wang Lei Jiang Donghao Zhang Likui |
| author_facet | Wang Lei Jiang Donghao Zhang Likui |
| author_sort | Wang Lei |
| collection | DOAJ |
| description | <?A3B2 tlsb=-.002w?>8-Oxoguanine (8oxoG) in DNA is a major oxidized base that poses a severe threat to genome stability. To counteract the mutagenic effect generated by 8oxoG in DNA, cells have evolved 8oxoG DNA glycosylase (OGG) that can excise this oxidized base from DNA. Currently, OGG enzymes have been divided into three families: OGG1, OGG2 and AGOG (archaeal 8oxoG DNA glycosylase). Due to the limited reports, our understanding on AGOG enzymes remains incomplete. Herein, we present evidence that an AGOG from the hyperthermophilic euryarchaeon Thermo Coccus barophilus Ch5 (Tb-AGOG) excises 8oxoG from DNA at high temperature. The enzyme displays maximum efficiency at 75°C–95°C and at pH 9.0. As expected, Tb-AGOG is a bifunctional glycosylase that harbors glycosylase activity and AP (apurinic/apyrimidinic) lyase activity. Importantly, we reveal for the first time that residue D41 in Tb-AGOG is essential for 8oxoG excision and intermediate formation, but not essential for DNA binding or AP cleavage. Furthermore, residue E79 in Tb-AGOG is essential for 8oxoG excision and intermediate formation, and is partially involved in DNA binding and AP cleavage, which has not been described among the reported AGOG members to date. Overall, our work provides new insights into catalytic mechanism of AGOG enzymes. <?A3B2 tlsb?> |
| first_indexed | 2024-03-11T12:20:24Z |
| format | Article |
| id | doaj.art-05863ca4aba048c7ad1e1c04986fd4d7 |
| institution | Directory Open Access Journal |
| issn | 1672-9145 |
| language | English |
| last_indexed | 2024-03-11T12:20:24Z |
| publishDate | 2022-06-01 |
| publisher | China Science Publishing & Media Ltd. |
| record_format | Article |
| series | Acta Biochimica et Biophysica Sinica |
| spelling | doaj.art-05863ca4aba048c7ad1e1c04986fd4d72023-11-07T01:02:58ZengChina Science Publishing & Media Ltd.Acta Biochimica et Biophysica Sinica1672-91452022-06-01541801181010.3724/abbs.202207220d259ccA thermophilic 8-oxoguanine DNA glycosylase from Thermococcus barophiluss Ch5 is a new member of AGOG DNA glycosylase familyWang Lei0Jiang Donghao1Zhang Likui2["College of Environmental Science and Engineering, Marine Science & Technology Institute, Yangzhou University, Yangzhou 225127, China"]["College of Environmental Science and Engineering, Marine Science & Technology Institute, Yangzhou University, Yangzhou 225127, China"]["College of Environmental Science and Engineering, Marine Science & Technology Institute, Yangzhou University, Yangzhou 225127, China","Guangling College, Yangzhou University, Yangzhou 225000, China"]<?A3B2 tlsb=-.002w?>8-Oxoguanine (8oxoG) in DNA is a major oxidized base that poses a severe threat to genome stability. To counteract the mutagenic effect generated by 8oxoG in DNA, cells have evolved 8oxoG DNA glycosylase (OGG) that can excise this oxidized base from DNA. Currently, OGG enzymes have been divided into three families: OGG1, OGG2 and AGOG (archaeal 8oxoG DNA glycosylase). Due to the limited reports, our understanding on AGOG enzymes remains incomplete. Herein, we present evidence that an AGOG from the hyperthermophilic euryarchaeon Thermo Coccus barophilus Ch5 (Tb-AGOG) excises 8oxoG from DNA at high temperature. The enzyme displays maximum efficiency at 75°C–95°C and at pH 9.0. As expected, Tb-AGOG is a bifunctional glycosylase that harbors glycosylase activity and AP (apurinic/apyrimidinic) lyase activity. Importantly, we reveal for the first time that residue D41 in Tb-AGOG is essential for 8oxoG excision and intermediate formation, but not essential for DNA binding or AP cleavage. Furthermore, residue E79 in Tb-AGOG is essential for 8oxoG excision and intermediate formation, and is partially involved in DNA binding and AP cleavage, which has not been described among the reported AGOG members to date. Overall, our work provides new insights into catalytic mechanism of AGOG enzymes. <?A3B2 tlsb?>https://www.sciengine.com/doi/10.3724/abbs.2022072hyperthermophilic Archaea8-oxoguanine8oxoG DNA glycosylasebiochemical characteristicbase excision repair |
| spellingShingle | Wang Lei Jiang Donghao Zhang Likui A thermophilic 8-oxoguanine DNA glycosylase from Thermococcus barophiluss Ch5 is a new member of AGOG DNA glycosylase family Acta Biochimica et Biophysica Sinica hyperthermophilic Archaea 8-oxoguanine 8oxoG DNA glycosylase biochemical characteristic base excision repair |
| title | A thermophilic 8-oxoguanine DNA glycosylase from Thermococcus barophiluss Ch5 is a new member of AGOG DNA glycosylase family |
| title_full | A thermophilic 8-oxoguanine DNA glycosylase from Thermococcus barophiluss Ch5 is a new member of AGOG DNA glycosylase family |
| title_fullStr | A thermophilic 8-oxoguanine DNA glycosylase from Thermococcus barophiluss Ch5 is a new member of AGOG DNA glycosylase family |
| title_full_unstemmed | A thermophilic 8-oxoguanine DNA glycosylase from Thermococcus barophiluss Ch5 is a new member of AGOG DNA glycosylase family |
| title_short | A thermophilic 8-oxoguanine DNA glycosylase from Thermococcus barophiluss Ch5 is a new member of AGOG DNA glycosylase family |
| title_sort | thermophilic 8 oxoguanine dna glycosylase from thermococcus barophiluss ch5 is a new member of agog dna glycosylase family |
| topic | hyperthermophilic Archaea 8-oxoguanine 8oxoG DNA glycosylase biochemical characteristic base excision repair |
| url | https://www.sciengine.com/doi/10.3724/abbs.2022072 |
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