PRMT5 Inhibitor EPZ015666 Decreases the Viability and Encystment of <i>Entamoeba invadens</i>
Protein arginine methyltransferase 5 (PRMT5) is an enzyme that produces monomethyl arginine (MMA) and symmetric dimethyl arginine (sDMA), post-translational modifications that regulate several cellular processes, including stage conversion in parasitic protozoans. <i>Entamoeba histolytica</...
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MDPI AG
2024-12-01
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| author | Rigoberto Ortiz-Hernández Elmer Joel Millán-Casarrubias Jeni Bolaños Susana Munguía-Robledo Carlos Vázquez-Calzada Elisa Azuara-Licéaga Jesús Valdés Mario Alberto Rodríguez |
| author_facet | Rigoberto Ortiz-Hernández Elmer Joel Millán-Casarrubias Jeni Bolaños Susana Munguía-Robledo Carlos Vázquez-Calzada Elisa Azuara-Licéaga Jesús Valdés Mario Alberto Rodríguez |
| author_sort | Rigoberto Ortiz-Hernández |
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| description | Protein arginine methyltransferase 5 (PRMT5) is an enzyme that produces monomethyl arginine (MMA) and symmetric dimethyl arginine (sDMA), post-translational modifications that regulate several cellular processes, including stage conversion in parasitic protozoans. <i>Entamoeba histolytica</i>, the etiologic agent of human amebiasis, has two stages in its life cycle, the trophozoite, which is the replicative form, and the cyst, corresponding to the infective phase. The study of the molecular mechanisms that regulate differentiation in this parasite has been overdue because of a lack of efficient protocols for in vitro encystment. For this reason, <i>Entamoeba invadens</i>, a parasite of reptiles, has been used as a differentiation model system for the genus. Here, we demonstrated the presence of sDMA in <i>E. invadens</i>, which increases during encystment, and identified the PRMT5 of this microorganism (EiPRMT5). In addition, we performed 3D modeling of this enzyme, as well as its molecular docking with the PRMT5 inhibitor EPZ015666, which predicted the affinity of the drug for the active site of the enzyme. In agreement with these findings, EPZ015666 reduced trophozoite viability and encystment. Therefore, EiPRMT5 is a potential target for inhibiting the spread of amebiasis. |
| format | Article |
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| institution | Kabale University |
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| language | English |
| publishDate | 2024-12-01 |
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| series | Molecules |
| spelling | doaj-art-bbb722d16e5a4e3f942860a4e6e910582025-01-10T13:18:45ZengMDPI AGMolecules1420-30492024-12-013016210.3390/molecules30010062PRMT5 Inhibitor EPZ015666 Decreases the Viability and Encystment of <i>Entamoeba invadens</i>Rigoberto Ortiz-Hernández0Elmer Joel Millán-Casarrubias1Jeni Bolaños2Susana Munguía-Robledo3Carlos Vázquez-Calzada4Elisa Azuara-Licéaga5Jesús Valdés6Mario Alberto Rodríguez7Departamento de Infectómica y Patogénesis Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City 07360, MexicoLaboratorio de Sistemas de Diagnóstico y Tratamiento de Cáncer, Unidad Profesional Interdisciplinaria en Ingeniería y Tecnologías Avanzadas del Instituto Politécnico Nacional, Mexico City 07340, MexicoDepartamento de Infectómica y Patogénesis Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City 07360, MexicoDepartamento de Infectómica y Patogénesis Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City 07360, MexicoDepartamento de Infectómica y Patogénesis Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City 07360, MexicoPrograma de Posgraduados en Ciencias Genómicas, Universidad Autónoma de la Ciudad de México, Mexico City 04510, MexicoDepartamento de Bioquímica, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City 07360, MexicoDepartamento de Infectómica y Patogénesis Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City 07360, MexicoProtein arginine methyltransferase 5 (PRMT5) is an enzyme that produces monomethyl arginine (MMA) and symmetric dimethyl arginine (sDMA), post-translational modifications that regulate several cellular processes, including stage conversion in parasitic protozoans. <i>Entamoeba histolytica</i>, the etiologic agent of human amebiasis, has two stages in its life cycle, the trophozoite, which is the replicative form, and the cyst, corresponding to the infective phase. The study of the molecular mechanisms that regulate differentiation in this parasite has been overdue because of a lack of efficient protocols for in vitro encystment. For this reason, <i>Entamoeba invadens</i>, a parasite of reptiles, has been used as a differentiation model system for the genus. Here, we demonstrated the presence of sDMA in <i>E. invadens</i>, which increases during encystment, and identified the PRMT5 of this microorganism (EiPRMT5). In addition, we performed 3D modeling of this enzyme, as well as its molecular docking with the PRMT5 inhibitor EPZ015666, which predicted the affinity of the drug for the active site of the enzyme. In agreement with these findings, EPZ015666 reduced trophozoite viability and encystment. Therefore, EiPRMT5 is a potential target for inhibiting the spread of amebiasis.https://www.mdpi.com/1420-3049/30/1/62<i>Entamoeba invadens</i>encystmentsymmetric arginine dimethylationPRMT5 |
| spellingShingle | Rigoberto Ortiz-Hernández Elmer Joel Millán-Casarrubias Jeni Bolaños Susana Munguía-Robledo Carlos Vázquez-Calzada Elisa Azuara-Licéaga Jesús Valdés Mario Alberto Rodríguez PRMT5 Inhibitor EPZ015666 Decreases the Viability and Encystment of <i>Entamoeba invadens</i> Molecules <i>Entamoeba invadens</i> encystment symmetric arginine dimethylation PRMT5 |
| title | PRMT5 Inhibitor EPZ015666 Decreases the Viability and Encystment of <i>Entamoeba invadens</i> |
| title_full | PRMT5 Inhibitor EPZ015666 Decreases the Viability and Encystment of <i>Entamoeba invadens</i> |
| title_fullStr | PRMT5 Inhibitor EPZ015666 Decreases the Viability and Encystment of <i>Entamoeba invadens</i> |
| title_full_unstemmed | PRMT5 Inhibitor EPZ015666 Decreases the Viability and Encystment of <i>Entamoeba invadens</i> |
| title_short | PRMT5 Inhibitor EPZ015666 Decreases the Viability and Encystment of <i>Entamoeba invadens</i> |
| title_sort | prmt5 inhibitor epz015666 decreases the viability and encystment of i entamoeba invadens i |
| topic | <i>Entamoeba invadens</i> encystment symmetric arginine dimethylation PRMT5 |
| url | https://www.mdpi.com/1420-3049/30/1/62 |
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