Substrate binding and catalytic mechanism of the Se-glycosyltransferase SenB in the biosynthesis of selenoneine
Abstract Selenium is an essential multifunctional trace element in diverse organisms. The only Se-glycosyltransferase identified that catalyzes the incorporation of selenium in selenoneine biosynthesis is SenB from Variovorax paradoxus. Although the biochemical function of SenB has been investigated...
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| Format: | Article |
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Nature Portfolio
2024-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-46065-6 |
| _version_ | 1797273892834770944 |
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| author | Wei Huang Jun Song Tianxue Sun Yue He Xiang Li Zixin Deng Feng Long |
| author_facet | Wei Huang Jun Song Tianxue Sun Yue He Xiang Li Zixin Deng Feng Long |
| author_sort | Wei Huang |
| collection | DOAJ |
| description | Abstract Selenium is an essential multifunctional trace element in diverse organisms. The only Se-glycosyltransferase identified that catalyzes the incorporation of selenium in selenoneine biosynthesis is SenB from Variovorax paradoxus. Although the biochemical function of SenB has been investigated, its substrate specificity, structure, and catalytic mechanism have not been elucidated. Here, we reveal that SenB exhibits sugar donor promiscuity and can utilize six UDP-sugars to generate selenosugars. We report crystal structures of SenB complexed with different UDP-sugars. The key elements N20/T23/E231 contribute to the sugar donor selectivity of SenB. A proposed catalytic mechanism is tested by structure-guided mutagenesis, revealing that SenB yields selenosugars by forming C-Se glycosidic bonds via spontaneous deprotonation and disrupting Se-P bonds by nucleophilic water attack, which is initiated by the critical residue K158. Furthermore, we functionally and structurally characterize two other Se-glycosyltransferases, CbSenB from Comamonadaceae bacterium and RsSenB from Ramlibacter sp., which also exhibit sugar donor promiscuity. |
| first_indexed | 2024-03-07T14:50:38Z |
| format | Article |
| id | doaj.art-7e579f2b17b343e7862741f6e9fd33a2 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-07T14:50:38Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-7e579f2b17b343e7862741f6e9fd33a22024-03-05T19:43:55ZengNature PortfolioNature Communications2041-17232024-02-0115111010.1038/s41467-024-46065-6Substrate binding and catalytic mechanism of the Se-glycosyltransferase SenB in the biosynthesis of selenoneineWei Huang0Jun Song1Tianxue Sun2Yue He3Xiang Li4Zixin Deng5Feng Long6Department of Neurosurgery, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan UniversityDepartment of Neurosurgery, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan UniversityMinistry of Education Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, School of Pharmaceutical Sciences, Wuhan UniversityMinistry of Education Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, School of Pharmaceutical Sciences, Wuhan UniversityDepartment of Neurosurgery, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan UniversityMinistry of Education Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, School of Pharmaceutical Sciences, Wuhan UniversityDepartment of Neurosurgery, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan UniversityAbstract Selenium is an essential multifunctional trace element in diverse organisms. The only Se-glycosyltransferase identified that catalyzes the incorporation of selenium in selenoneine biosynthesis is SenB from Variovorax paradoxus. Although the biochemical function of SenB has been investigated, its substrate specificity, structure, and catalytic mechanism have not been elucidated. Here, we reveal that SenB exhibits sugar donor promiscuity and can utilize six UDP-sugars to generate selenosugars. We report crystal structures of SenB complexed with different UDP-sugars. The key elements N20/T23/E231 contribute to the sugar donor selectivity of SenB. A proposed catalytic mechanism is tested by structure-guided mutagenesis, revealing that SenB yields selenosugars by forming C-Se glycosidic bonds via spontaneous deprotonation and disrupting Se-P bonds by nucleophilic water attack, which is initiated by the critical residue K158. Furthermore, we functionally and structurally characterize two other Se-glycosyltransferases, CbSenB from Comamonadaceae bacterium and RsSenB from Ramlibacter sp., which also exhibit sugar donor promiscuity.https://doi.org/10.1038/s41467-024-46065-6 |
| spellingShingle | Wei Huang Jun Song Tianxue Sun Yue He Xiang Li Zixin Deng Feng Long Substrate binding and catalytic mechanism of the Se-glycosyltransferase SenB in the biosynthesis of selenoneine Nature Communications |
| title | Substrate binding and catalytic mechanism of the Se-glycosyltransferase SenB in the biosynthesis of selenoneine |
| title_full | Substrate binding and catalytic mechanism of the Se-glycosyltransferase SenB in the biosynthesis of selenoneine |
| title_fullStr | Substrate binding and catalytic mechanism of the Se-glycosyltransferase SenB in the biosynthesis of selenoneine |
| title_full_unstemmed | Substrate binding and catalytic mechanism of the Se-glycosyltransferase SenB in the biosynthesis of selenoneine |
| title_short | Substrate binding and catalytic mechanism of the Se-glycosyltransferase SenB in the biosynthesis of selenoneine |
| title_sort | substrate binding and catalytic mechanism of the se glycosyltransferase senb in the biosynthesis of selenoneine |
| url | https://doi.org/10.1038/s41467-024-46065-6 |
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