{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T09:10:55Z","timestamp":1786612255337,"version":"build-2736575974"},"reference-count":33,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2017,10,26]],"date-time":"2017-10-26T00:00:00Z","timestamp":1508976000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Glucose-6-phosphate dehydrogenase (G6PD) is a key regulatory enzyme that plays a crucial role in the regulation of cellular energy and redox balance. Mutations in the gene encoding G6PD cause the most common enzymopathy that drives hereditary nonspherocytic hemolytic anemia. To gain insights into the effects of mutations in G6PD enzyme efficiency, we have investigated the biochemical, kinetic, and structural changes of three clinical G6PD variants, the single mutations G6PD A+ (Asn126AspD) and G6PD Nefza (Leu323Pro), and the double mutant G6PD A\u2212 (Asn126Asp + Leu323Pro). The mutants showed lower residual activity (\u226450% of WT G6PD) and displayed important kinetic changes. Although all Class III mutants were located in different regions of the three-dimensional structure of the enzyme and were not close to the active site, these mutants had a deleterious effect over catalytic activity and structural stability. The results indicated that the G6PD Nefza mutation was mainly responsible for the functional and structural alterations observed in the double mutant G6PD A\u2212. Moreover, our study suggests that the G6PD Nefza and G6PD A\u2212 mutations affect enzyme functions in a similar fashion to those reported for Class I mutations.<\/jats:p>","DOI":"10.3390\/ijms18112244","type":"journal-article","created":{"date-parts":[[2017,10,26]],"date-time":"2017-10-26T06:48:14Z","timestamp":1509000494000},"page":"2244","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Biochemical Analysis of Two Single Mutants that Give Rise to a Polymorphic G6PD A-Double Mutant"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1166-190X","authenticated-orcid":false,"given":"Edson","family":"Ram\u00edrez-Nava","sequence":"first","affiliation":[{"name":"Laboratorio de Bioqu\u00edmica Gen\u00e9tica, Instituto Nacional de Pediatr\u00eda, Secretar\u00eda de Salud, Mexico City 04530, 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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7901-475X","authenticated-orcid":false,"given":"Hugo","family":"Serrano-Posada","sequence":"additional","affiliation":[{"name":"Consejo Nacional de Ciencia y Tecnolog\u00eda (CONACYT), Laboratorio de Agrobiotecnolog\u00eda, Tecnoparque CLQ, Universidad de Colima, Carretera los Limones-Loma de Ju\u00e1rez, Colima 28629, 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"}]},{"given":"America","family":"Vanoye-Carlo","sequence":"additional","affiliation":[{"name":"Laboratorio de Neurociencias, Instituto Nacional de Pediatr\u00eda, Secretar\u00eda de Salud, Mexico City 04530, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3939-6930","authenticated-orcid":false,"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":"Edgar","family":"Sierra-Palacios","sequence":"additional","affiliation":[{"name":"Colegio de Ciencias y Humanidades, Plantel Casa Libertad, Universidad Aut\u00f3noma de la Ciudad de M\u00e9xico, Mexico City 09620, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Hern\u00e1ndez-Pineda","sequence":"additional","affiliation":[{"name":"Departamento de Infectolog\u00eda e Inmunolog\u00eda, Instituto Nacional de Perinatolog\u00eda, Secretar\u00eda de Salud, Mexico City 11000, M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Rodr\u00edguez-Bustamante","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica de Biomacromol\u00e9culas, Instituto de Qu\u00edmica, Universidad Nacional Aut\u00f3noma de Mexico, 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 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