{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:36:38Z","timestamp":1760146598589,"version":"build-2065373602"},"reference-count":49,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T00:00:00Z","timestamp":1732233600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Recursos Fiscales para la Investigaci\u00f3n, E022 Program","award":["034\/2022","TKII-AMVL001"],"award-info":[{"award-number":["034\/2022","TKII-AMVL001"]}]},{"name":"HIM\/2019\/036 SSA. 1595","award":["034\/2022","TKII-AMVL001"],"award-info":[{"award-number":["034\/2022","TKII-AMVL001"]}]},{"name":"National Supercomputing Center\u2014IPICYT","award":["034\/2022","TKII-AMVL001"],"award-info":[{"award-number":["034\/2022","TKII-AMVL001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an enzymopathy that affects approximately 500 million people worldwide. A great number of mutations in the G6PD gene have been described. However, three class A G6PD variants known as G6PD Tomah (C385R), G6PD Kangnam (C385G), and G6PD Madrid (C385W) have been reported to be clinically important due to their associations with severe clinical manifestations such as hemolytic anemia. Therefore, this work aimed to perform, for the first time, biochemical and functional characterizations of these variants. The G6PD variants were cloned and purified for this purpose, followed by analyses of their kinetic parameters and thermal stability, as well as in silico studies. The results showed that the mutations induced changes in the proteins. Regarding the kinetic parameters, it was observed that the three variants showed lower affinities for G6P and NADP+, as well as lower thermal stability compared to WT-G6PD. Molecular dynamics simulations showed that C385 mutations induced changes around neighboring amino acids. Metadynamics simulations showed that most remarkable changes account for the binding pocket volumes, particularly in the structural NADP+ binding site, with a concomitant loss of affinity for catalytic processes.<\/jats:p>","DOI":"10.3390\/ijms252312556","type":"journal-article","created":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T06:41:48Z","timestamp":1732257708000},"page":"12556","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Evaluation of Three Mutations in Codon 385 of Glucose-6-Phosphate Dehydrogenase via Biochemical and In Silico Analysis"],"prefix":"10.3390","volume":"25","author":[{"given":"Adriana","family":"G\u00e1lvez-Ram\u00edrez","sequence":"first","affiliation":[{"name":"Laboratorio de Bioqu\u00edmica Gen\u00e9tica, Instituto Nacional de Pediatr\u00eda, Secretar\u00eda de Salud, Mexico City 04530, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5694-3118","authenticated-orcid":false,"given":"Luis Miguel","family":"Canseco-\u00c1vila","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias Qu\u00edmicas, Campus IV, Universidad Aut\u00f3noma de Chiapas, Tapachula City 30580, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3697-4523","authenticated-orcid":false,"given":"Alexander","family":"L\u00f3pez-Roblero","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias Qu\u00edmicas, Campus IV, Universidad Aut\u00f3noma de Chiapas, Tapachula City 30580, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Hern\u00e1ndez-Urzua","sequence":"additional","affiliation":[{"name":"Laboratorio de Toxicolog\u00eda Gen\u00e9tica, Instituto Nacional de Pediatr\u00eda, Secretar\u00eda de Salud, Mexico City 04530, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6580-3440","authenticated-orcid":false,"given":"Noemi","family":"C\u00e1rdenas-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Laboratorio de Neurociencias, Instituto Nacional de Pediatri\u0301a, Secretari\u0301a de Salud, Mexico City 04530, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2058-5707","authenticated-orcid":false,"given":"Sergio","family":"Enr\u00edquez-Flores","sequence":"additional","affiliation":[{"name":"Laboratorio de Biomol\u00e9culas y Salud Infantil, Instituto Nacional de Pediatr\u00eda, Secretar\u00eda de Salud, Mexico City 04530, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5654-8089","authenticated-orcid":false,"given":"Ignacio","family":"De la Mora-De la Mora","sequence":"additional","affiliation":[{"name":"Laboratorio de Biomol\u00e9culas y Salud Infantil, Instituto Nacional de Pediatr\u00eda, Secretar\u00eda de Salud, Mexico City 04530, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5674-7881","authenticated-orcid":false,"given":"Abraham","family":"Vidal-Limon","sequence":"additional","affiliation":[{"name":"Red de Estudios Moleculares Avanzados, Cl\u00faster Cient\u00edfico y Tecnol\u00f3gico BioMimic, Instituto de Ecolog\u00eda A.C. (INECOL), Carretera Antigua a Coatepec 351, El Haya, Xalapa 91073, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2095-9182","authenticated-orcid":false,"given":"Sa\u00fal","family":"G\u00f3mez-Manzo","sequence":"additional","affiliation":[{"name":"Laboratorio de Bioqu\u00edmica Gen\u00e9tica, Instituto Nacional de Pediatr\u00eda, Secretar\u00eda de Salud, Mexico City 04530, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1104\/pp.107.108423","article-title":"Functional Analyses of Cytosolic Glucose-6-Phosphate Dehydrogenases and Their Contribution to Seed Oil Accumulation in Arabidopsis","volume":"146","author":"Wakao","year":"2008","journal-title":"Plant Physiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1104\/pp.103.025676","article-title":"Differential Regulation of Glucose-6-Phosphate Dehydrogenase Isoenzyme Activities in Potato","volume":"133","author":"Hauschild","year":"2003","journal-title":"Plant Physiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.plaphy.2016.04.013","article-title":"Glucose-6-phosphate dehydrogenase plays a central role in the response of tomato (Solanum lycopersicum) plants to short and long-term drought","volume":"105","author":"Landi","year":"2016","journal-title":"Plant Physiol. 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