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Exploring the Ascorbate Requirement of the 2-Oxoglutarate-Dependent Dioxygenases.
J Med Chem
January 2025
Ma̅tai Ha̅ora - Centre for Redox Biology and Medicine, Department of Biomedical Science and Pathology, University of Otago, Christchurch, Christchurch 8140, New Zealand.
In humans, the 2-oxoglutarate-dependent dioxygenases (2-OGDDs) catalyze hydroxylation reactions involved in cell metabolism, the biosynthesis of small molecules, DNA and RNA demethylation, the hypoxic response and the formation of collagen. The reaction is catalyzed by a highly oxidizing ferryl-oxo species produced when the active site non-heme iron engages molecular oxygen. Enzyme activity is specifically stimulated by l-ascorbic acid (ascorbate, vitamin C), an effect not well mimicked by other reducing agents.
View Article and Find Full Text PDFConformational dynamics of a multienzyme complex in anaerobic carbon fixation.
Science
January 2025
Redox and Metalloprotein Research Group, Max Planck Institute of Biophysics, Frankfurt am Main, Germany.
In the ancient microbial Wood-Ljungdahl pathway, carbon dioxide (CO) is fixed in a multistep process that ends with acetyl-coenzyme A (acetyl-CoA) synthesis at the bifunctional carbon monoxide dehydrogenase/acetyl-CoA synthase complex (CODH/ACS). In this work, we present structural snapshots of the CODH/ACS from the gas-converting acetogen , characterizing the molecular choreography of the overall reaction, including electron transfer to the CODH for CO reduction, methyl transfer from the corrinoid iron-sulfur protein (CoFeSP) partner to the ACS active site, and acetyl-CoA production. Unlike CODH, the multidomain ACS undergoes large conformational changes to form an internal connection to the CODH active site, accommodate the CoFeSP for methyl transfer, and protect the reaction intermediates.
View Article and Find Full Text PDFInvestigating the miRNA-mRNA interactome of human trabecular meshwork cells treated with TGF-β1 provides insights into the pathogenesis of pseudoexfoliation glaucoma.
PLoS One
January 2025
Biomedical Sciences Research Institute, Centre for Genomic Medicine, Ulster University, Coleraine, Northern Ireland, United Kingdom.
Pseudoexfoliation glaucoma is a severe form of secondary open angle glaucoma and is associated with activation of the TGF-β pathway by TGF-β1. MicroRNAs (miRNAs) are small non-coding RNA species that are involved in regulation of mRNA expression and translation. To investigate what glaucomatous changes occur in the trabecular meshwork and how these changes may be regulated by miRNAs, we performed a bioinformatics analysis resulting in a miRNA-mRNA interactome.
View Article and Find Full Text PDFA new computational framework for simulating airway resistance, fraction of exhaled nitric oxide, and diffusing capacity for nitric oxide.
PLoS One
January 2025
Transfers, Interfaces and Processes, Université libre de Bruxelles, Brussels, Belgium.
In this paper, we present a new computational framework for the simulation of airway resistance, the fraction of exhaled nitric oxide, and the diffusion capacity for nitric oxide in healthy and unhealthy lungs. Our approach is firstly based on a realistic representation of the geometry of healthy lungs as a function of body mass, which compares well with data from the literature, particularly in terms of lung volume and alveolar surface area. The original way in which this geometry is created, including an individual definition of the airways in the first seven generations of the lungs, makes it possible to consider the heterogeneous nature of the lungs in terms of perfusion and ventilation.
View Article and Find Full Text PDFProteomics Reveals Mechanisms of Delayed Keratoconus Progression: A Study of Corneas Following Two Light-Activated Crosslinking Treatments.
Invest Ophthalmol Vis Sci
January 2025
University Eye Clinic Maastricht, Maastricht University Medical Center, Maastricht, the Netherlands.
Article Synopsis
- This study investigates the biological changes in rabbit corneas caused by two light-activated corneal stiffening methods: riboflavin with UVA and WST11 with NIR.
- Differentially expressed proteins were identified following treatments, showing RF-D/UVA affected cell metabolism and keratocyte differentiation, while WST-D/NIR influenced extracellular matrix regulation.
- The findings reveal a metabolic shift towards glycolysis in RF-D/UVA treated corneas compared to normal respiration in WST-D/NIR treated corneas, highlighting the distinct biological effects of each treatment.
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