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Flavin-Mediated Reductive Deiodination: Conformational Events and Reactivity Pattern in the Active Site of Human Iodotyrosine Deiodinase.
Biochemistry
December 2024
Department of Chemistry, Indian Institute of Technology Kharagpur, Kharagpur 721302, West Bengal, India.
Human iodotyrosine deiodinase (hIYD) catalyzes the reductive deiodination of iodotyrosine using a flavin mononucleotide cofactor to maintain the iodine concentration in the body. Mutations in the hIYD gene are linked to human hypothyroidism, emphasizing its role in thyroid function regulation. The present work employs microsecond-scale molecular dynamics simulations and quantum chemical calculations to elucidate the conformational dynamics and reactivity in the active site at various stages of hIYD enzymatic cycle.
View Article and Find Full Text PDFMisregulation of bromotyrosine compromises fertility in male .
Proc Natl Acad Sci U S A
May 2024
Department of Chemistry, The Johns Hopkins University, Baltimore, MD 21218.
Biological regulation often depends on reversible reactions such as phosphorylation, acylation, methylation, and glycosylation, but rarely halogenation. A notable exception is the iodination and deiodination of thyroid hormones. Here, we report detection of bromotyrosine and its subsequent debromination during spermatogenesis.
View Article and Find Full Text PDFPeroxidasin Inhibition by Phloroglucinol and Other Peroxidase Inhibitors.
Antioxidants (Basel)
December 2023
Institute of Biochemistry, Department of Chemistry, University of Natural Resources and Life Sciences, Vienna, Muthgasse 18, 1190 Vienna, Austria.
Human peroxidasin (PXDN) is a ubiquitous peroxidase enzyme expressed in most tissues in the body. PXDN represents an interesting therapeutic target for inhibition, as it plays a role in numerous pathologies, including cardiovascular disease, cancer and fibrosis. Like other peroxidases, PXDN generates hypohalous acids and free radical species, thereby facilitating oxidative modifications of numerous biomolecules.
View Article and Find Full Text PDF: Over- or Under-Iodination Risk in the Prophylactic Use of Iodine for Thyroid Blocking in the Event of a Nuclear Disaster.
Front Endocrinol (Lausanne)
June 2022
Pediatric Department, "Vittore Buzzi" Children's Hospital, Milan, Italy.
Iodine is an essential element for the production of thyroid hormones (THs). Both deficient and excess iodine intakes may precipitate in adverse thyroidal events. Radioactive iodine (RI) is a common byproduct of nuclear fission processes.
View Article and Find Full Text PDFHalogenation Activity of Mammalian Heme Peroxidases.
Antioxidants (Basel)
April 2022
Gottfried Schatz Research Center, Division of Molecular Biology and Biochemistry, Medical University of Graz, 8010 Graz, Austria.
Mammalian heme peroxidases are fascinating due to their unique peculiarity of oxidizing (pseudo)halides under physiologically relevant conditions. These proteins are able either to incorporate oxidized halides into substrates adjacent to the active site or to generate different oxidized (pseudo)halogenated species, which can take part in multiple (pseudo)halogenation and oxidation reactions with cell and tissue constituents. The present article reviews basic biochemical and redox mechanisms of (pseudo)halogenation activity as well as the physiological role of heme peroxidases.
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