{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T05:29:42Z","timestamp":1789450182952,"version":"build-2803163510"},"reference-count":35,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2014,11,17]],"date-time":"2014-11-17T00:00:00Z","timestamp":1416182400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","award":["154570"],"award-info":[{"award-number":["154570"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","award":["106126"],"award-info":[{"award-number":["106126"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","award":["62321"],"award-info":[{"award-number":["62321"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","award":["157863"],"award-info":[{"award-number":["157863"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","award":["2184"],"award-info":[{"award-number":["2184"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Instituto Nacional de Pediatria Fondos Federales","award":["089\/2012"],"award-info":[{"award-number":["089\/2012"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme deficiency worldwide, causing a wide spectrum of conditions with severity classified from the mildest (Class IV) to the most severe (Class I). To correlate mutation sites in the G6PD with the resulting phenotypes, we studied four naturally occurring G6PD variants: Yucatan, Nashville, Valladolid and Mexico City. For this purpose, we developed a successful over-expression method that constitutes an easier and more precise method for obtaining and characterizing these enzymes. The kcat (catalytic constant) of all the studied variants was lower than in the wild-type. The structural rigidity might be the cause and the most evident consequence of the mutations is their impact on protein stability and folding, as can be observed from the protein yield, the T50 (temperature where 50% of its  original activity is retained) values, and differences on hydrophobic regions. The mutations corresponding to more severe phenotypes are related to the structural NADP+ region.  This was clearly observed for the Classes III and II variants, which became more thermostable with increasing NADP+, whereas the Class I variants remained thermolabile. The mutations produce repulsive electric charges that, in the case of the Yucatan variant, promote increased disorder of the C-terminus and consequently affect the binding of NADP+, leading to enzyme instability.<\/jats:p>","DOI":"10.3390\/ijms151121179","type":"journal-article","created":{"date-parts":[[2014,11,17]],"date-time":"2014-11-17T10:19:13Z","timestamp":1416219553000},"page":"21179-21201","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["The Stability of G6PD Is Affected by Mutations with Different Clinical Phenotypes"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2095-9182","authenticated-orcid":false,"given":"Sa\u00fal","family":"G\u00f3mez-Manzo","sequence":"first","affiliation":[{"name":"Laboratorio de Bioqu\u00edmica Gen\u00e9tica, Instituto Nacional de Pediatr\u00eda, M\u00e9xico D.F. 04530, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Terr\u00f3n-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Laboratorio de Bioqu\u00edmica Gen\u00e9tica, Instituto Nacional de Pediatr\u00eda, M\u00e9xico D.F. 04530, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignacio","family":"De la Mora-De la Mora","sequence":"additional","affiliation":[{"name":"Laboratorio de Bioqu\u00edmica Gen\u00e9tica, Instituto Nacional de Pediatr\u00eda, M\u00e9xico D.F. 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, M\u00e9xico D.F. 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime","family":"Marcial-Quino","sequence":"additional","affiliation":[{"name":"CONACyT, Instituto Nacional de Pediatr\u00eda, M\u00e9xico D.F. 04530, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Itzhel","family":"Garc\u00eda-Torres","sequence":"additional","affiliation":[{"name":"Laboratorio de Bioqu\u00edmica Gen\u00e9tica, Instituto Nacional de Pediatr\u00eda, M\u00e9xico D.F. 04530, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"America","family":"Vanoye-Carlo","sequence":"additional","affiliation":[{"name":"Laboratorio de Bioqu\u00edmica Gen\u00e9tica, Instituto Nacional de Pediatr\u00eda, M\u00e9xico D.F. 04530, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"L\u00f3pez-Vel\u00e1zquez","sequence":"additional","affiliation":[{"name":"Laboratorio de Bioqu\u00edmica Gen\u00e9tica, Instituto Nacional de Pediatr\u00eda, M\u00e9xico D.F. 04530, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Hern\u00e1ndez-Alc\u00e1ntara","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica, Facultad de Medicina, Universidad Nacional Aut\u00f3noma de M\u00e9xico, M\u00e9xico D.F. 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas","family":"Oria-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Laboratorio de Bioqu\u00edmica Gen\u00e9tica, Instituto Nacional de Pediatr\u00eda, M\u00e9xico D.F. 04530, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Horacio","family":"Reyes-Vivas","sequence":"additional","affiliation":[{"name":"Laboratorio de Bioqu\u00edmica Gen\u00e9tica, Instituto Nacional de Pediatr\u00eda, M\u00e9xico D.F. 04530, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Enr\u00edquez-Flores","sequence":"additional","affiliation":[{"name":"Laboratorio de Bioqu\u00edmica Gen\u00e9tica, Instituto Nacional de Pediatr\u00eda, M\u00e9xico D.F. 04530, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2014,11,17]]},"reference":[{"key":"ref_1","first-page":"4517","article-title":"Glucose-6-phosphate dehydrogenase deficiency","volume":"Volume 179","author":"Scriver","year":"2001","journal-title":"Metabolic and Molecular Bases of Inherited Disease"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1182\/blood.V73.1.334.334","article-title":"Catalase and glutathione peroxidase are equally active in detoxification of hydrogen peroxide in human erythrocytes","volume":"73","author":"Gaetani","year":"1989","journal-title":"Blood"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1006\/bcmd.1997.0147","article-title":"Hematologically important mutations: Glucose-6-phosphate dehydrogenase","volume":"23","author":"Vulliamy","year":"1997","journal-title":"Blood Cells Mol. 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