ArticleProceedings of the National Academy of Sciences of the United States of America2018
Crystal structure of human mARC1 reveals its exceptional position among eukaryotic molybdenum enzymes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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32 citing papers in PubMed, 56 citations in OpenAlex.
- Genetics of MASLD: a diabetes perspective.Diabetologia · 2026Review
- Genetic and genomic insights across the steatotic liver disease spectrum.Clinical and molecular hepatology · 2026Review
- Metabolic dysfunction-associated steatotic liver disease: pathogenesis and novel treatment options.Molecular biomedicine · 2026Review
- Genetic modulators of metabolic dysfunction-associated steatotic liver disease (MASLD) and their epistatic interactions: from in vitro and animal models to clinical outcomes.BMC medical genomics · 2026Review
- A mitochondrial amidoxime-reducing component 1 (mARC1) A168T amino acid substitution does not confer protection from MASH and fibrosis in multiple mouse models of chronic liver disease.The Biochemical journal · 2026Article
- Human genetics of metabolic dysfunction-associated steatotic liver disease: from variants to cause to precision treatment.The Journal of clinical investigation · 2025Review
- Precision medicine and nucleotide-based therapeutics to treat steatotic liver disease.Clinical and molecular hepatology · 2025Review
- Nitrite Reductases in Biomedicine: From Natural Enzymes to Artificial Mimics.Research (Washington, D.C.) · 2025Review
- mARC1 Is the Main Contributor to Metabolic Reduction ofJournal of medicinal chemistry · 2024Article
- Convergent evolution links molybdenum insertase domains with organism-specific sequences.Communications biology · 2024Article
- Second-Coordination-Sphere Effects Reveal Electronic Structure Differences between the Mitochondrial Amidoxime Reducing Component and Sulfite Oxidase.Inorganic chemistry · 2024Article
- Letter regarding 'mitochondrial amidoxime-reducing component 1 p.Ala165Thr increases protein degradation mediated by the proteasome'.Liver international : official journal of the International Association for the Study of the Liver · 2024Article
- Molybdenum's Role as an Essential Element in Enzymes Catabolizing Redox Reactions: A Review.Biomolecules · 2024Review
- Fatty liver disease protective MTARC1 p.A165T variant reduces the protein stability of MTARC1.Biochemical and biophysical research communications · 2024Article
- Divergent role of Mitochondrial Amidoxime Reducing Component 1 (MARC1) in human and mouse.PLoS genetics · 2024Article
- Advancing Our Understanding of Pyranopterin-Dithiolene Contributions to Moco Enzyme Catalysis.Molecules (Basel, Switzerland) · 2023Review
- Reduction of Hydrogen Peroxide by Human Mitochondrial Amidoxime Reducing Component Enzymes.Molecules (Basel, Switzerland) · 2023Article
- Does the Micronutrient Molybdenum Have a Role in Gestational Complications and Placental Health?Nutrients · 2023Review
- The History of mARC.Molecules (Basel, Switzerland) · 2023Review
- Hepatocyte mARC1 promotes fatty liver disease.JHEP reports : innovation in hepatology · 2023Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Biotransformation enzymes ensure a viable homeostasis by regulating reversible cycles of oxidative and reductive reactions. The metabolism of nitrogen-containing compounds is of high pharmaceutical and toxicological relevance because N-oxygenated metabolites derived from reactions mediated by cytochrome P450 enzymes or flavin-dependent monooxygenases are in some cases highly toxic or mutagenic. The molybdenum-dependent mitochondrial amidoxime-reducing component (mARC) was found to be an extremely efficient counterpart, which is able to reduce the full range of N-oxygenated compounds and thereby mediates detoxification reactions. However, the 3D structure of this enzyme was unknown. Here we present the high-resolution crystal structure of human mARC. We give detailed insight into the coordination of its molybdenum cofactor (Moco), the catalytic mechanism, and its ability to reduce a wide range of N-oxygenated compounds. The identification of two key residues will allow future discrimination between mARC paralogs and ensure correct annotation. Since our structural findings contradict in silico predictions that are currently made by online databases, we propose domain definitions for members of the superfamily of Moco sulfurase C-terminal (MOSC) domain-containing proteins. Furthermore, we present evidence for an evolutionary role of mARC for the emergence of the xanthine oxidase protein superfamily. We anticipate the hereby presented crystal structure to be a starting point for future descriptions of MOSC proteins, which are currently poorly structurally characterized.
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