First characterization of a microsporidial triosephosphate isomerase and the biochemical mechanisms of its inactivation to propose a new druggable target
| Autor: | Gabriela Nava, Silvia Caballero-Salazar, Sergio Enríquez-Flores, Gloria Hernández-Alcántara, Alfonso Olivos-García, Gabriel López-Velázquez, Dora Molina-Ortiz, Itzhel García-Torres, Ignacio de la Mora-de la Mora |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Drug Gastrointestinal Diseases media_common.quotation_subject Druggability lcsh:Medicine Biology Albendazole Microsporidiosis Gene Expression Regulation Enzymologic Microbiology Triosephosphate isomerase Fungal Proteins 03 medical and health sciences Gene Expression Regulation Fungal medicine Humans Amino Acid Sequence Thiamine lcsh:Science media_common chemistry.chemical_classification Multidisciplinary Sequence Homology Amino Acid Intracellular parasite lcsh:R Encephalitozoon medicine.disease biology.organism_classification Encephalitozoon intestinalis 030104 developmental biology Enzyme chemistry Rabeprazole Microsporidia lcsh:Q Omeprazole Triose-Phosphate Isomerase |
| Zdroj: | Scientific Reports, Vol 8, Iss 1, Pp 1-12 (2018) |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-018-26845-z |
| Popis: | The microsporidia are a large group of intracellular parasites with a broad range of hosts, including humans. Encephalitozoon intestinalis is the second microsporidia species most frequently associated with gastrointestinal disease in humans, especially immunocompromised or immunosuppressed individuals, including children and the elderly. The prevalence reported worldwide in these groups ranges from 0 to 60%. Currently, albendazole is most commonly used to treat microsporidiosis caused by Encephalitozoon species. However, the results of treatment are variable, and relapse can occur. Consequently, efforts are being directed toward identifying more effective drugs for treating microsporidiosis, and the study of new molecular targets appears promising. These parasites lack mitochondria, and oxidative phosphorylation therefore does not occur, which suggests the enzymes involved in glycolysis as potential drug targets. Here, we have for the first time characterized the glycolytic enzyme triosephosphate isomerase of E. intestinalis at the functional and structural levels. Our results demonstrate the mechanisms of inactivation of this enzyme by thiol-reactive compounds. The most striking result of this study is the demonstration that established safe drugs such as omeprazole, rabeprazole and sulbutiamine can effectively inactivate this microsporidial enzyme and might be considered as potential drugs for treating this important disease. |
| Databáze: | OpenAIRE |
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