Theoretical Study of Sphingomyelinases from <i>Entamoeba histolytica</i> and <i>Trichomonas vaginalis</i> Sheds Light on the Evolution of Enzymes Needed for Survival and Colonization
The path to survival for pathogenic organisms is not straightforward. Pathogens require a set of enzymes for tissue damage generation and to obtain nourishment, as well as a toolbox full of alternatives to bypass host defense mechanisms. Our group has shown that the parasitic protist <i>Entamo...
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2025-01-01
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| author | Fátima Berenice Ramírez-Montiel Sairy Yarely Andrade-Guillen Ana Laura Medina-Nieto Ángeles Rangel-Serrano José A. Martínez-Álvarez Javier de la Mora Naurú Idalia Vargas-Maya Claudia Leticia Mendoza-Macías Felipe Padilla-Vaca Bernardo Franco |
| author_facet | Fátima Berenice Ramírez-Montiel Sairy Yarely Andrade-Guillen Ana Laura Medina-Nieto Ángeles Rangel-Serrano José A. Martínez-Álvarez Javier de la Mora Naurú Idalia Vargas-Maya Claudia Leticia Mendoza-Macías Felipe Padilla-Vaca Bernardo Franco |
| author_sort | Fátima Berenice Ramírez-Montiel |
| collection | DOAJ |
| description | The path to survival for pathogenic organisms is not straightforward. Pathogens require a set of enzymes for tissue damage generation and to obtain nourishment, as well as a toolbox full of alternatives to bypass host defense mechanisms. Our group has shown that the parasitic protist <i>Entamoeba histolytica</i> encodes for 14 sphingomyelinases (SMases); one of them (acid sphingomyelinase 6, aSMase6) is involved in repairing membrane damage and exhibits hemolytic activity. The enzymatic characterization of aSMase6 has been shown to be activated by magnesium ions but not by zinc, as shown for the human aSMase, and is strongly inhibited by cobalt. However, no structural data are available for the aSMase6 enzyme. In this work, bioinformatic analyses showed that the protist aSMases are diverse enzymes, are evolutionarily related to hemolysins derived from bacteria, and showed a similar overall structure as parasitic, free-living protists and mammalian enzymes. AlphaFold3 models predicted the occupancy of cobalt ions in the active site of the aSMase6 enzyme. Cavity blind docking showed that the substrate is pushed outward of the active site when cobalt is bound instead of magnesium ions. Additionally, the structural models of the aSMase6 of <i>E. histolytica</i> showed a loop that is absent from the rest of the aSMases, suggesting that it may be involved in hemolytic activity, as demonstrated experimentally using the recombinant proteins of aSMase4 and aSMase6. <i>Trichomonas vaginalis</i> enzymes show a putative transmembrane domain and seem functionally different from <i>E. histolytica</i>. This work provides insight into the future biochemical analyses that can show mechanistic features of parasitic protists sphingomyelinases, ultimately rendering these enzymes potential therapeutic targets. |
| format | Article |
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| institution | Kabale University |
| issn | 2076-0817 |
| language | English |
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| spelling | doaj-art-045414f32a5f4c42a6b5c545f30560ea2025-01-24T13:44:40ZengMDPI AGPathogens2076-08172025-01-011413210.3390/pathogens14010032Theoretical Study of Sphingomyelinases from <i>Entamoeba histolytica</i> and <i>Trichomonas vaginalis</i> Sheds Light on the Evolution of Enzymes Needed for Survival and ColonizationFátima Berenice Ramírez-Montiel0Sairy Yarely Andrade-Guillen1Ana Laura Medina-Nieto2Ángeles Rangel-Serrano3José A. Martínez-Álvarez4Javier de la Mora5Naurú Idalia Vargas-Maya6Claudia Leticia Mendoza-Macías7Felipe Padilla-Vaca8Bernardo Franco9Departamento de Farmacia, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Noria Alta s/n, Guanajuato 36050, MexicoDepartamento de Biología, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Noria Alta s/n, Guanajuato 36050, MexicoDepartamento de Biología, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Noria Alta s/n, Guanajuato 36050, MexicoDepartamento de Biología, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Noria Alta s/n, Guanajuato 36050, MexicoDepartamento de Biología, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Noria Alta s/n, Guanajuato 36050, MexicoGenética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City 04510, MexicoDepartamento de Biología, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Noria Alta s/n, Guanajuato 36050, MexicoDepartamento de Biología, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Noria Alta s/n, Guanajuato 36050, MexicoDepartamento de Biología, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Noria Alta s/n, Guanajuato 36050, MexicoDepartamento de Biología, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Noria Alta s/n, Guanajuato 36050, MexicoThe path to survival for pathogenic organisms is not straightforward. Pathogens require a set of enzymes for tissue damage generation and to obtain nourishment, as well as a toolbox full of alternatives to bypass host defense mechanisms. Our group has shown that the parasitic protist <i>Entamoeba histolytica</i> encodes for 14 sphingomyelinases (SMases); one of them (acid sphingomyelinase 6, aSMase6) is involved in repairing membrane damage and exhibits hemolytic activity. The enzymatic characterization of aSMase6 has been shown to be activated by magnesium ions but not by zinc, as shown for the human aSMase, and is strongly inhibited by cobalt. However, no structural data are available for the aSMase6 enzyme. In this work, bioinformatic analyses showed that the protist aSMases are diverse enzymes, are evolutionarily related to hemolysins derived from bacteria, and showed a similar overall structure as parasitic, free-living protists and mammalian enzymes. AlphaFold3 models predicted the occupancy of cobalt ions in the active site of the aSMase6 enzyme. Cavity blind docking showed that the substrate is pushed outward of the active site when cobalt is bound instead of magnesium ions. Additionally, the structural models of the aSMase6 of <i>E. histolytica</i> showed a loop that is absent from the rest of the aSMases, suggesting that it may be involved in hemolytic activity, as demonstrated experimentally using the recombinant proteins of aSMase4 and aSMase6. <i>Trichomonas vaginalis</i> enzymes show a putative transmembrane domain and seem functionally different from <i>E. histolytica</i>. This work provides insight into the future biochemical analyses that can show mechanistic features of parasitic protists sphingomyelinases, ultimately rendering these enzymes potential therapeutic targets.https://www.mdpi.com/2076-0817/14/1/32sphingomyelinases<i>Entamoeba histolytica</i><i>Trichomonas vaginalis</i>evolutionstructural featuresAlphaFold3 |
| spellingShingle | Fátima Berenice Ramírez-Montiel Sairy Yarely Andrade-Guillen Ana Laura Medina-Nieto Ángeles Rangel-Serrano José A. Martínez-Álvarez Javier de la Mora Naurú Idalia Vargas-Maya Claudia Leticia Mendoza-Macías Felipe Padilla-Vaca Bernardo Franco Theoretical Study of Sphingomyelinases from <i>Entamoeba histolytica</i> and <i>Trichomonas vaginalis</i> Sheds Light on the Evolution of Enzymes Needed for Survival and Colonization Pathogens sphingomyelinases <i>Entamoeba histolytica</i> <i>Trichomonas vaginalis</i> evolution structural features AlphaFold3 |
| title | Theoretical Study of Sphingomyelinases from <i>Entamoeba histolytica</i> and <i>Trichomonas vaginalis</i> Sheds Light on the Evolution of Enzymes Needed for Survival and Colonization |
| title_full | Theoretical Study of Sphingomyelinases from <i>Entamoeba histolytica</i> and <i>Trichomonas vaginalis</i> Sheds Light on the Evolution of Enzymes Needed for Survival and Colonization |
| title_fullStr | Theoretical Study of Sphingomyelinases from <i>Entamoeba histolytica</i> and <i>Trichomonas vaginalis</i> Sheds Light on the Evolution of Enzymes Needed for Survival and Colonization |
| title_full_unstemmed | Theoretical Study of Sphingomyelinases from <i>Entamoeba histolytica</i> and <i>Trichomonas vaginalis</i> Sheds Light on the Evolution of Enzymes Needed for Survival and Colonization |
| title_short | Theoretical Study of Sphingomyelinases from <i>Entamoeba histolytica</i> and <i>Trichomonas vaginalis</i> Sheds Light on the Evolution of Enzymes Needed for Survival and Colonization |
| title_sort | theoretical study of sphingomyelinases from i entamoeba histolytica i and i trichomonas vaginalis i sheds light on the evolution of enzymes needed for survival and colonization |
| topic | sphingomyelinases <i>Entamoeba histolytica</i> <i>Trichomonas vaginalis</i> evolution structural features AlphaFold3 |
| url | https://www.mdpi.com/2076-0817/14/1/32 |
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