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Cited by 17Organoselenium and organotellurium chemistrySelenium in Biological SystemsGlycosylation and Glycoproteins Research

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Substrate binding and catalytic mechanism of the Se-glycosyltransferase SenB in the biosynthesis of selenoneine

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Huang, Wei, Song, Jun, Sun, Tianxue, He, Yue, Li, Xiang, Deng, Zixin, Long, Feng·2024·Nature Communications
DOI 10.1038/s41467-024-46065-6PMC PMC10891094

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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, Cb SenB from Comamonadaceae bacterium and Rs SenB from Ramlibacter sp., which also exhibit sugar donor promiscuity.

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Metadata

Authors
Huang, W., Song, J., Sun, T., He, Y., Li, X., Deng, Z., & Long, F.
Affiliations
Wuhan University (CN)
Corresponding author
Long, Feng
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2024-02-23
Volume
15
Issue
1
Pages
1659-1659
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-024-46065-6
PMC
PMC10891094
OpenAlex
W4392097227
Cited by
17
References
1
Citations by year
2026: 4 · 2025: 8 · 2024: 5
FWCI
4.03
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • National Natural Science Foundation of China (82304333)
  • Wuhan University
  • Yangzhou University
  • Zhongnan Hospital of Wuhan University (CXPY2023011, ZNJC202245)
  • National Key Research and Development Program of China (2021YFA0909500)
  • Fundamental Research Funds for the Central Universities (BL19U1, 2042019kf0185)
Topics
  • Physical Sciences › Chemistry › Organic Chemistry › Organoselenium and organotellurium chemistry
  • Health Sciences › Nursing › Nutrition and Dietetics › Selenium in Biological Systems
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
Keywords
selenium incorporation, substrate specificity, UDP-sugars, selenosugars, catalytic mechanism, crystal structure, Variovorax paradoxus, Comamonadaceae, Ramlibacter
MeSH terms
Sugars, Carbohydrates, Histidine, Selenium, Substrate Specificity, Uridine Diphosphate Sugars, Organoselenium Compounds, Glycosyltransferases

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