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Activation of nitrofurazone by azoreductases: multiple activities in one enzyme
Azoreductases are well known for azo pro-drug activation by gut flora. We show that azoreductases have a wider role in drug metabolism than previously thought as they can also reduce and hence activate nitrofurazone. Nitrofurazone, a nitroaromatic drug, is a broad spectrum antibiotic which has until...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3216550/ https://www.ncbi.nlm.nih.gov/pubmed/22355582 http://dx.doi.org/10.1038/srep00063 |
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author | Ryan, Ali Kaplan, Elise Laurieri, Nicola Lowe, Edward Sim, Edith |
author_facet | Ryan, Ali Kaplan, Elise Laurieri, Nicola Lowe, Edward Sim, Edith |
author_sort | Ryan, Ali |
collection | PubMed |
description | Azoreductases are well known for azo pro-drug activation by gut flora. We show that azoreductases have a wider role in drug metabolism than previously thought as they can also reduce and hence activate nitrofurazone. Nitrofurazone, a nitroaromatic drug, is a broad spectrum antibiotic which has until now been considered as activated in bacteria by nitroreductases. The structure of the azoreductase with nitrofurazone bound was solved at 2.08 Å and shows nitrofurazone in an active conformation. Based on the structural information, the kinetics and stoichiometry of nitrofurazone reduction by azoreductase from P. aeruginosa, we propose a mechanism of activation which accounts for the ability of azoreductases to reduce both azo and nitroaromatic drugs. This mode of activation can explain the cytotoxic side-effects of nitrofurazone through human azoreductase homologues. |
format | Online Article Text |
id | pubmed-3216550 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-32165502011-12-22 Activation of nitrofurazone by azoreductases: multiple activities in one enzyme Ryan, Ali Kaplan, Elise Laurieri, Nicola Lowe, Edward Sim, Edith Sci Rep Article Azoreductases are well known for azo pro-drug activation by gut flora. We show that azoreductases have a wider role in drug metabolism than previously thought as they can also reduce and hence activate nitrofurazone. Nitrofurazone, a nitroaromatic drug, is a broad spectrum antibiotic which has until now been considered as activated in bacteria by nitroreductases. The structure of the azoreductase with nitrofurazone bound was solved at 2.08 Å and shows nitrofurazone in an active conformation. Based on the structural information, the kinetics and stoichiometry of nitrofurazone reduction by azoreductase from P. aeruginosa, we propose a mechanism of activation which accounts for the ability of azoreductases to reduce both azo and nitroaromatic drugs. This mode of activation can explain the cytotoxic side-effects of nitrofurazone through human azoreductase homologues. Nature Publishing Group 2011-08-12 /pmc/articles/PMC3216550/ /pubmed/22355582 http://dx.doi.org/10.1038/srep00063 Text en Copyright © 2011, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by-nc-sa/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-ShareALike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/ |
spellingShingle | Article Ryan, Ali Kaplan, Elise Laurieri, Nicola Lowe, Edward Sim, Edith Activation of nitrofurazone by azoreductases: multiple activities in one enzyme |
title | Activation of nitrofurazone by azoreductases: multiple activities in one enzyme |
title_full | Activation of nitrofurazone by azoreductases: multiple activities in one enzyme |
title_fullStr | Activation of nitrofurazone by azoreductases: multiple activities in one enzyme |
title_full_unstemmed | Activation of nitrofurazone by azoreductases: multiple activities in one enzyme |
title_short | Activation of nitrofurazone by azoreductases: multiple activities in one enzyme |
title_sort | activation of nitrofurazone by azoreductases: multiple activities in one enzyme |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3216550/ https://www.ncbi.nlm.nih.gov/pubmed/22355582 http://dx.doi.org/10.1038/srep00063 |
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