| Autor: |
Raoul Manuel, Michelle de Souza Lima, Sébastien Dilly, Sylvain Daunay, Patricia Abbe, Elodie Pramil, Stéphanie Solier, Fabienne Guillaumond, Sarah-Simha Tubiana, Alexandre Escargueil, João Antonio Pêgas Henriques, Nathalie Ferrand, Irène Erdelmeier, Jean-Luc Boucher, Gildas Bertho, Israel Agranat, Stéphane Rocchi, Michèle Sabbah, Anny Slama Schwok |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
Antioxidants, Vol 10, Iss 5, p 723 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2076-3921 |
| DOI: |
10.3390/antiox10050723 |
| Popis: |
Specific inhibition of NADPH oxidases (NOX) and NO-synthases (NOS), two enzymes associated with redox stress in tumor cells, has aroused great pharmacological interest. Here, we show how these enzymes distinguish between isomeric 2′- and 3′-phosphate derivatives, a difference used to improve the specificity of inhibition by isolated 2′- and 3′-phosphate isomers of our NADPH analogue NS1. Both isomers become fluorescent upon binding to their target proteins as observed by in vitro assay and in vivo imaging. The 2′-phosphate isomer of NS1 exerted more pronounced effects on NOS and NOX-dependent physiological responses than the 3′-phosphate isomer did. Docking and molecular dynamics simulations explain this specificity at the level of the NADPH site of NOX and NOS, where conserved arginine residues distinguished between the 2′-phosphate over the 3′-phosphate group, in favor of the 2′-phosphate. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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