{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T20:04:25Z","timestamp":1787774665586,"version":"build-2784847793"},"reference-count":65,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2023,7,15]],"date-time":"2023-07-15T00:00:00Z","timestamp":1689379200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"E022 Program, National Institute of Pediatrics, Mexico City, Mexico (Recursos Fiscales para la Investigaci\u00f3n)","award":["TKII-AMVL001"],"award-info":[{"award-number":["TKII-AMVL001"]}]},{"name":"INP 021\/2022","award":["TKII-AMVL001"],"award-info":[{"award-number":["TKII-AMVL001"]}]},{"name":"HIM\/2019\/036 SSA. 1595","award":["TKII-AMVL001"],"award-info":[{"award-number":["TKII-AMVL001"]}]},{"name":"National Supercomputing Center\u2013IPICYT for the computational resources","award":["TKII-AMVL001"],"award-info":[{"award-number":["TKII-AMVL001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Giardiasis, which is caused by Giardia lamblia infection, is a relevant cause of morbidity and mortality worldwide. Because no vaccines are currently available to treat giardiasis, chemotherapeutic drugs are the main options for controlling infection. Evidence has shown that the nitro drug nitazoxanide (NTZ) is a commonly prescribed treatment for giardiasis; however, the mechanisms underlying NTZ\u2019s antigiardial activity are not well-understood. Herein, we identified the glucose-6-phosphate::6-phosphogluconate dehydrogenase (GlG6PD::6PGL) fused enzyme as a nitazoxanide target, as NTZ behaves as a GlG6PD::6PGL catalytic inhibitor. Furthermore, fluorescence assays suggest alterations in the stability of GlG6PD::6PGL protein, whereas the results indicate a loss of catalytic activity due to conformational and folding changes. Molecular docking and dynamic simulation studies suggest a model of NTZ binding on the active site of the G6PD domain and near the structural NADP+ binding site. The findings of this study provide a novel mechanistic basis and strategy for the antigiardial activity of the NTZ drug.<\/jats:p>","DOI":"10.3390\/ijms241411516","type":"journal-article","created":{"date-parts":[[2023,7,17]],"date-time":"2023-07-17T00:35:04Z","timestamp":1689554104000},"page":"11516","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Nitazoxanide Inhibits the Bifunctional Enzyme GlG6PD::6PGL of Giardia lamblia: Biochemical and In Silico Characterization of a New Druggable Target"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6137-6499","authenticated-orcid":false,"given":"V\u00edctor","family":"Mart\u00ednez-Rosas","sequence":"first","affiliation":[{"name":"Laboratorio de Bioqu\u00edmica Gen\u00e9tica, Instituto Nacional de Pediatr\u00eda, Secretar\u00eda de Salud, Mexico City 04530, Mexico"},{"name":"Programa de Posgrado en Biomedicina y Biotecnolog\u00eda Molecular, Escuela Nacional de Ciencias Biol\u00f3gicas, Instituto Polit\u00e9cnico Nacional, Mexico City 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Hern\u00e1ndez-Ochoa","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunoqu\u00edmica, Hospital Infantil de M\u00e9xico Federico G\u00f3mez, Secretar\u00eda de Salud, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Morales-Luna","sequence":"additional","affiliation":[{"name":"Laboratorio de Bioqu\u00edmica Gen\u00e9tica, Instituto Nacional de Pediatr\u00eda, Secretar\u00eda de Salud, Mexico City 04530, Mexico"},{"name":"Posgrado en Ciencias Biol\u00f3gicas, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7950-4911","authenticated-orcid":false,"given":"Daniel","family":"Ortega-Cuellar","sequence":"additional","affiliation":[{"name":"Laboratorio de Nutrici\u00f3n Experimental, Instituto Nacional de Pediatr\u00eda, Secretar\u00eda de Salud, Mexico City 04530, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail","family":"Gonz\u00e1lez-Valdez","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda Molecular y Biotecnolog\u00eda, Instituto de Investigaciones Biom\u00e9dicas, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4611-4770","authenticated-orcid":false,"given":"Roberto","family":"Arreguin-Espinosa","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica de Biomacromol\u00e9culas, Instituto de Qu\u00edmica, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8124-4482","authenticated-orcid":false,"given":"Yadira","family":"Rufino-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Laboratorio de Parasitolog\u00eda Experimental, Instituto Nacional de Pediatr\u00eda, Secretar\u00eda de Salud, Mexico City 04530, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernesto","family":"Calder\u00f3n-Jaimes","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunoqu\u00edmica, Hospital Infantil de M\u00e9xico Federico G\u00f3mez, Secretar\u00eda de Salud, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4117-6689","authenticated-orcid":false,"given":"Rosa Ang\u00e9lica","family":"Castillo-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"CICATA Unidad Morelos, Instituto Polit\u00e9cnico Nacional, Boulevard de la Tecnolog\u00eda, 1036 Z-1, P 2\/2, Atlacholoaya 62790, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6262-8106","authenticated-orcid":false,"given":"Carlos","family":"Wong-Baeza","sequence":"additional","affiliation":[{"name":"Laboratorio de Biomembranas, Departamento de Bioqu\u00edmica, Escuela Nacional de Ciencias Biol\u00f3gicas, Instituto Polit\u00e9cnico Nacional, Mexico City 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Baeza-Ram\u00edrez","sequence":"additional","affiliation":[{"name":"Laboratorio de Biomembranas, Departamento de Bioqu\u00edmica, Escuela Nacional de Ciencias Biol\u00f3gicas, Instituto Polit\u00e9cnico Nacional, Mexico City 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1451-8754","authenticated-orcid":false,"given":"Ver\u00f3nica","family":"P\u00e9rez de la Cruz","sequence":"additional","affiliation":[{"name":"Neurobiochemistry and Behavior Laboratory, National Institute of Neurology and Neurosurgery \u201cManuel Velasco Su\u00e1rez\u201d, Mexico City 14269, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5674-7881","authenticated-orcid":false,"given":"Abraham","family":"Vidal-Lim\u00f3n","sequence":"additional","affiliation":[{"name":"Red de Estudios Moleculares Avanzados, Cl\u00faster Cient\u00edfico y Tecnol\u00f3gico BioMimic\u00ae, Instituto de Ecolog\u00eda A.C. 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