An enzymatic activation of formaldehyde for nucleotide methylation
The bacterial thymidylate synthase ThyX catalyzes the reductive methylation of deoxyuridylate (dUMP) into deoxythymidylate (dTMP) and requires both folate and flavin for activity. Here, the authors combine biochemical experiments, spectroscopic measurements and flavin synthesis chemistry to show tha...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-021-24756-8 |
| _version_ | 1818997717667414016 |
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| author | Charles Bou-Nader Frederick W. Stull Ludovic Pecqueur Philippe Simon Vincent Guérineau Antoine Royant Marc Fontecave Murielle Lombard Bruce A. Palfey Djemel Hamdane |
| author_facet | Charles Bou-Nader Frederick W. Stull Ludovic Pecqueur Philippe Simon Vincent Guérineau Antoine Royant Marc Fontecave Murielle Lombard Bruce A. Palfey Djemel Hamdane |
| author_sort | Charles Bou-Nader |
| collection | DOAJ |
| description | The bacterial thymidylate synthase ThyX catalyzes the reductive methylation of deoxyuridylate (dUMP) into deoxythymidylate (dTMP) and requires both folate and flavin for activity. Here, the authors combine biochemical experiments, spectroscopic measurements and flavin synthesis chemistry to show that formaldehyde (CH2O) can replace the natural methylene donor of ThyX in a CH2O-shunt reaction, yielding a carbinolamine intermediate with the reduced flavin coenzyme, and they present the crystal structure of this intermediate. |
| first_indexed | 2024-12-20T21:50:04Z |
| format | Article |
| id | doaj.art-9d2804fa1f2e4892889a444777040660 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-12-20T21:50:04Z |
| publishDate | 2021-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-9d2804fa1f2e4892889a4447770406602022-12-21T19:25:34ZengNature PortfolioNature Communications2041-17232021-07-011211810.1038/s41467-021-24756-8An enzymatic activation of formaldehyde for nucleotide methylationCharles Bou-Nader0Frederick W. Stull1Ludovic Pecqueur2Philippe Simon3Vincent Guérineau4Antoine Royant5Marc Fontecave6Murielle Lombard7Bruce A. Palfey8Djemel Hamdane9Laboratoire de Chimie des Processus Biologiques, CNRS-UMR 8229, Collège De France, Université Pierre et Marie CuriePrograms in Chemical Biology and the Department of Biological Chemistry, University of Michigan Medical SchoolLaboratoire de Chimie des Processus Biologiques, CNRS-UMR 8229, Collège De France, Université Pierre et Marie CurieLaboratoire de Chimie des Processus Biologiques, CNRS-UMR 8229, Collège De France, Université Pierre et Marie CurieCNRS, Institut de Chimie des Substances Naturelles UPR 2301, Université Paris-SaclayCEA, CNRS, Institut de Biologie Structurale (IBS), Université Grenoble AlpesLaboratoire de Chimie des Processus Biologiques, CNRS-UMR 8229, Collège De France, Université Pierre et Marie CurieLaboratoire de Chimie des Processus Biologiques, CNRS-UMR 8229, Collège De France, Université Pierre et Marie CuriePrograms in Chemical Biology and the Department of Biological Chemistry, University of Michigan Medical SchoolLaboratoire de Chimie des Processus Biologiques, CNRS-UMR 8229, Collège De France, Université Pierre et Marie CurieThe bacterial thymidylate synthase ThyX catalyzes the reductive methylation of deoxyuridylate (dUMP) into deoxythymidylate (dTMP) and requires both folate and flavin for activity. Here, the authors combine biochemical experiments, spectroscopic measurements and flavin synthesis chemistry to show that formaldehyde (CH2O) can replace the natural methylene donor of ThyX in a CH2O-shunt reaction, yielding a carbinolamine intermediate with the reduced flavin coenzyme, and they present the crystal structure of this intermediate.https://doi.org/10.1038/s41467-021-24756-8 |
| spellingShingle | Charles Bou-Nader Frederick W. Stull Ludovic Pecqueur Philippe Simon Vincent Guérineau Antoine Royant Marc Fontecave Murielle Lombard Bruce A. Palfey Djemel Hamdane An enzymatic activation of formaldehyde for nucleotide methylation Nature Communications |
| title | An enzymatic activation of formaldehyde for nucleotide methylation |
| title_full | An enzymatic activation of formaldehyde for nucleotide methylation |
| title_fullStr | An enzymatic activation of formaldehyde for nucleotide methylation |
| title_full_unstemmed | An enzymatic activation of formaldehyde for nucleotide methylation |
| title_short | An enzymatic activation of formaldehyde for nucleotide methylation |
| title_sort | enzymatic activation of formaldehyde for nucleotide methylation |
| url | https://doi.org/10.1038/s41467-021-24756-8 |
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