The mitochondrial amidoxime reducing component-from prodrug-activation mechanism to drug-metabolizing enzyme and onward to drug target.
| Autor: | Struwe MA; Zoologisches Institut - Strukturbiologie, Christian-Albrechts-Universität Kiel, Kiel, Germany; Pharmazeutisches Institut, Christian-Albrechts-Universität Kiel, Kiel, Germany. Electronic address: mstruwe@strubio.uni-kiel.de., Scheidig AJ; Zoologisches Institut - Strukturbiologie, Christian-Albrechts-Universität Kiel, Kiel, Germany., Clement B; Pharmazeutisches Institut, Christian-Albrechts-Universität Kiel, Kiel, Germany. |
|---|---|
| Jazyk: | angličtina |
| Zdroj: | The Journal of biological chemistry [J Biol Chem] 2023 Nov; Vol. 299 (11), pp. 105306. Date of Electronic Publication: 2023 Sep 29. |
| DOI: | 10.1016/j.jbc.2023.105306 |
| Abstrakt: | The mitochondrial amidoxime-reducing component (mARC) is one of five known molybdenum enzymes in eukaryotes. mARC belongs to the MOSC domain superfamily, a large group of so far poorly studied molybdoenzymes. mARC was initially discovered as the enzyme activating N-hydroxylated prodrugs of basic amidines but has since been shown to also reduce a variety of other N-oxygenated compounds, for example, toxic nucleobase analogs. Under certain circumstances, mARC might also be involved in reductive nitric oxide synthesis through reduction of nitrite. Recently, mARC enzymes have received a lot of attention due to their apparent involvement in lipid metabolism and, in particular, because many genome-wide association studies have shown a common variant of human mARC1 to have a protective effect against liver disease. The mechanism linking mARC enzymes with lipid metabolism remains unknown. Here, we give a comprehensive overview of what is currently known about mARC enzymes, their substrates, structure, and apparent involvement in human disease. Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.) |
| Databáze: | MEDLINE |
| Externí odkaz: |
|