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Mechanistic insights into the ROS-mediated inactivation of human aldehyde oxidase |
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| Author: | Esmaeeli, Mariam1; Nimtz, Manfred2; Jänsch, Lothar2; |
| Organizations: |
1Department of Molecular Enzymology, Institute of Biochemistry and Biology, University of Potsdam, Germany 2Helmholtz Center for Infection Research, Braunschweig, Germany 3Faculty of Biochemistry and Molecular Medicine, University of Oulu, Finland |
| Format: | article |
| Version: | accepted version |
| Access: | embargoed |
| Persistent link: | http://urn.fi/urn:nbn:fi-fe20230914125437 |
| Language: | English |
| Published: |
John Wiley & Sons,
2023
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| Publish Date: | 2024-07-10 |
| Description: |
AbstractHuman aldehyde oxidase (hAOX1) is a molybdoenzyme that oxidizes aldehydes and N-heterocyclic compounds, thereby generating hydrogen peroxide (H₂O₂) and superoxide during turnover. hAOX1 has been shown previously to be inactivated under turnover conditions by H₂O₂. Here, we investigated the effect of exogenously added H₂O₂ on the activity of hAOX1. We show that exogenously added H₂O₂ did not affect the enzyme activity under aerobic conditions, but completely inactivated the enzyme under anaerobic conditions. We propose that this effect is based on the reducing power of H₂O₂ and the susceptibility of the reduced molybdenum cofactor (Moco) to lose the sulfido ligand. When oxygen is present, the enzyme is rapidly reoxidized. We believe that our study is significant in understanding the detailed effect of reactive oxygen species on the inactivation of hAOX1 and other molybdoenzymes. see all
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| Series: |
FEBS letters |
| ISSN: | 0014-5793 |
| ISSN-E: | 1873-3468 |
| ISSN-L: | 0014-5793 |
| Volume: | 597 |
| Issue: | 13 |
| Pages: | 1792 - 1801 |
| DOI: | 10.1002/1873-3468.14669 |
| OADOI: | https://oadoi.org/10.1002/1873-3468.14669 |
| Type of Publication: |
A1 Journal article – refereed |
| Field of Science: |
1182 Biochemistry, cell and molecular biology |
| Subjects: | |
| Funding: |
This work was supported by the Deutsche Forschungsgemeinschaft grant [LE1171/8-3]. |
| Copyright information: |
© 2023 Federation of European Biochemical Societies. This is the peer reviewed version of the following article: Esmaeeli, M., Nimtz, M., Jänsch, L., Ruddock, L.W. and Leimkühler, S. (2023), Mechanistic insights into the ROS-mediated inactivation of human aldehyde oxidase. FEBS Lett, 597: 1792-1801, which has been published in final form at https://doi.org/10.1002/1873-3468.14669. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited. |