The molybdenum cofactor (Moco) represents an ancient metal‑sulfur cofactor, which participates as catalyst in carbon, nitrogen and sulfur cycles, both on individual and global scale. Given the diversity of biological processes dependent on Moco and their evolutionary age, Moco is traced back to the last universal common ancestor (LUCA), while Moco biosynthetic genes underwent significant changes through evolution and acquired additional functions. In this review, focused on eukaryotic Moco biology, we elucidate the benefits of gene fusions on Moco biosynthesis and beyond. While originally the gene fusions were driven by biosynthetic advantages such as coordinated expression of functionally related proteins and product/substrate channeling, they also served as origin for the development of novel functions. Today, Moco biosynthetic genes are involved in a multitude of cellular processes and loss of the according gene products result in severe disorders, both related to Moco biosynthesis and secondary enzyme functions.
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http://dx.doi.org/10.1016/j.bbamcr.2020.118883 | DOI Listing |
Nat Commun
January 2025
Department of Pharmacology & Therapeutics, McGill University, 3655 Prom. Sir-William-Osler, Montreal, Quebec, H3G 1Y6, Canada.
Urolithin A (uroA) is a polyphenol derived from the multi-step metabolism of dietary ellagitannins by the human gut microbiota. Once absorbed, uroA can trigger mitophagy and aryl hydrocarbon receptor signaling pathways, altering host immune function, mitochondrial health, and intestinal barrier integrity. Most individuals harbor a microbiota capable of uroA production; however, the mechanisms underlying the dehydroxylation of its catechol-containing precursor (uroC) are unknown.
View Article and Find Full Text PDFCommun Biol
January 2025
Institut Pasteur, CNRS UMR 3528, Université Paris Cité, Structural Microbiology Unit, F-75015, Paris, France.
MoeA, also known as gephyrin in higher eukaryotes, is an enzyme essential for molybdenum cofactor (Moco) biosynthesis and involved in GABA and GlyR receptor clustering at the synapse in animals. We recently discovered that Actinobacteria have a repurposed version of MoeA (Glp) linked to bacterial cell division. Since MoeA exists in all domains of life, our study explores how it gained multifunctionality over time.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Molecular Enzymology, Institute of Biochemistry and Biology, University of Potsdam, Karl-Liebknecht Str. 24-25, 14476 Potsdam, Germany.
The enterobacterium present in the human gut can reduce trimethylamine N-oxide (TMAO) to trimethylamine during anaerobic respiration. The TMAO reductase TorA is a monomeric, bis-molybdopterin guanine dinucleotide (bis-MGD) cofactor-containing enzyme that belongs to the dimethyl sulfoxide reductase family of molybdoenzymes. TorA is anchored to the membrane via TorC, a pentahemic -type cytochrome which receives the electrons from the menaquinol pool.
View Article and Find Full Text PDFInorg Chem
January 2025
Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester M1 7DN, U.K.
Nitrogenase is the enzyme primarily responsible for reducing atmospheric nitrogen to ammonia. There are three general forms of nitrogenase based on the metal ion present in the cofactor binding site, namely, molybdenum-dependent nitrogenases with the iron-molybdenum cofactor (FeMoco), the vanadium-dependent nitrogenases with FeVco, and the iron-only nitrogenases. It has been shown that the vanadium-dependent nitrogenases tend to have a lesser efficacy in reducing dinitrogen but a higher efficacy in binding and reducing carbon monoxide.
View Article and Find Full Text PDFMetab Brain Dis
December 2024
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, Porto Alegre, 90035-003, RS, Brazil.
Sulfite oxidase deficiencies, either caused by deficiency of the apoenzyme or the molybdenum cofactor, and ethylmalonic encephalopathy are inherited disorders that impact sulfur metabolism. These patients present with severe neurodeterioration accompanied by cerebral cortex and cerebellum abnormalities, and high thiosulfate levels in plasma and tissues, including the brain. We aimed to clarify the mechanisms of such abnormalities, so we assessed the ex vivo effects of thiosulfate administration on energetic status and oxidative stress markers in cortical and cerebellar tissues of newborn rats.
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