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Human Orphan Cytochrome P450 2U1 Catalyzes the ω-Hydroxylation of Leukotriene B(4)
Cytochrome P450 2U1 (CYP2U1) identified from the human genome remains poorly known since few data are presently available on its physiological function(s) and substrate(s) specificity. CYP2U1 mutations are associated with complicated forms of hereditary spastic paraplegia, alterations of mitochondri...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9739833/ https://www.ncbi.nlm.nih.gov/pubmed/36498943 http://dx.doi.org/10.3390/ijms232314615 |
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author | Nouri, Khawla Pietrancosta, Nicolas Le Corre, Laurent Dansette, Patrick M. Mansuy, Daniel Boucher, Jean-Luc |
author_facet | Nouri, Khawla Pietrancosta, Nicolas Le Corre, Laurent Dansette, Patrick M. Mansuy, Daniel Boucher, Jean-Luc |
author_sort | Nouri, Khawla |
collection | PubMed |
description | Cytochrome P450 2U1 (CYP2U1) identified from the human genome remains poorly known since few data are presently available on its physiological function(s) and substrate(s) specificity. CYP2U1 mutations are associated with complicated forms of hereditary spastic paraplegia, alterations of mitochondrial architecture and bioenergetics. In order to better know the biological roles of CYP2U1, we used a bioinformatics approach. The analysis of the data invited us to focus on leukotriene B(4) (LTB(4)), an important inflammatory mediator. Here, we show that CYP2U1 efficiently catalyzes the hydroxylation of LTB(4) predominantly on its ω-position. We also report docking experiments of LTB(4) in a 3D model of truncated CYP2U1 that are in agreement with this hydroxylation regioselectivity. The involvement of CYP2U1 in the metabolism of LTB(4) could have strong physiological consequences in cerebral pathologies including ischemic stroke because CYP2U1 is predominantly expressed in the brain. |
format | Online Article Text |
id | pubmed-9739833 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-97398332022-12-11 Human Orphan Cytochrome P450 2U1 Catalyzes the ω-Hydroxylation of Leukotriene B(4) Nouri, Khawla Pietrancosta, Nicolas Le Corre, Laurent Dansette, Patrick M. Mansuy, Daniel Boucher, Jean-Luc Int J Mol Sci Communication Cytochrome P450 2U1 (CYP2U1) identified from the human genome remains poorly known since few data are presently available on its physiological function(s) and substrate(s) specificity. CYP2U1 mutations are associated with complicated forms of hereditary spastic paraplegia, alterations of mitochondrial architecture and bioenergetics. In order to better know the biological roles of CYP2U1, we used a bioinformatics approach. The analysis of the data invited us to focus on leukotriene B(4) (LTB(4)), an important inflammatory mediator. Here, we show that CYP2U1 efficiently catalyzes the hydroxylation of LTB(4) predominantly on its ω-position. We also report docking experiments of LTB(4) in a 3D model of truncated CYP2U1 that are in agreement with this hydroxylation regioselectivity. The involvement of CYP2U1 in the metabolism of LTB(4) could have strong physiological consequences in cerebral pathologies including ischemic stroke because CYP2U1 is predominantly expressed in the brain. MDPI 2022-11-23 /pmc/articles/PMC9739833/ /pubmed/36498943 http://dx.doi.org/10.3390/ijms232314615 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Communication Nouri, Khawla Pietrancosta, Nicolas Le Corre, Laurent Dansette, Patrick M. Mansuy, Daniel Boucher, Jean-Luc Human Orphan Cytochrome P450 2U1 Catalyzes the ω-Hydroxylation of Leukotriene B(4) |
title | Human Orphan Cytochrome P450 2U1 Catalyzes the ω-Hydroxylation of Leukotriene B(4) |
title_full | Human Orphan Cytochrome P450 2U1 Catalyzes the ω-Hydroxylation of Leukotriene B(4) |
title_fullStr | Human Orphan Cytochrome P450 2U1 Catalyzes the ω-Hydroxylation of Leukotriene B(4) |
title_full_unstemmed | Human Orphan Cytochrome P450 2U1 Catalyzes the ω-Hydroxylation of Leukotriene B(4) |
title_short | Human Orphan Cytochrome P450 2U1 Catalyzes the ω-Hydroxylation of Leukotriene B(4) |
title_sort | human orphan cytochrome p450 2u1 catalyzes the ω-hydroxylation of leukotriene b(4) |
topic | Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9739833/ https://www.ncbi.nlm.nih.gov/pubmed/36498943 http://dx.doi.org/10.3390/ijms232314615 |
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