Biochemical analysis of two single mutants that give rise to a polymorphic G6PD A-double mutant
Por:
Jiovany Ramirez-Nava, Edson, Ortega-Cuellar, Daniel, Serrano-Posada, Hugo, Gonzalez-Valdez, Abigail, Vanoye-Carlo, America, Hernandez-Ochoa, Beatriz, Sierra-Palacios, Edgar, Hernandez-Pineda, Jessica, Rodriguez-Bustamante, Eduardo, Arreguin-Espinosa, Roberto, Oria-Hernandez, Jesus, Reyes-Vivas, Horacio, Marcial-Quino, Jaime, Gomez-Manzo, Saul
Publicada:
1 nov 2017
Resumen:
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- (Asn126Asp + Leu323Pro). The mutants showed lower residual activity (=50% 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-. Moreover, our study suggests that the G6PD Nefza and G6PD A- mutations affect enzyme functions in a similar fashion to those reported for Class I mutations. © 2017 by the authors. Licensee MDPI, Basel, Switzerland.
Filiaciones:
Jiovany Ramirez-Nava, Edson:
Secretaria Salud Mexico, Inst Nacl Pediat, Lab Bioquim Genet, Mexico City 04530, DF, Mexico
Ortega-Cuellar, Daniel:
Secretaria Salud Mexico, Inst Nacl Pediat, Lab Nutr Expt, Mexico City 04530, DF, Mexico
Serrano-Posada, Hugo:
Univ Colima, Lab Agrobiotecnol, Consejo Nacl Ciencia Tecnol CONACYT, Tecnoparque CLQ, Carretera Limones Loma de Juarez, Colima 28629, Mexico
Gonzalez-Valdez, Abigail:
Univ Nacl Autonoma Mexico, Inst Invest Biomed, Dept Biol Mol & Biotecnol, Mexico City 04510, DF, Mexico
Vanoye-Carlo, America:
Secretaria Salud Mexico, Lab Neurociencias, Inst Nacl Pediat, Mexico City 04530, DF, Mexico
Hernandez-Ochoa, Beatriz:
Secretaria Salud Mexico, Lab Inmunoquim, Hosp Infantil Mexico Federico Gomez, Mexico City 06720, DF, Mexico
Sierra-Palacios, Edgar:
Univ Autonoma Ciudad Mexico, Colegio Ciencias & Humanidades, Plantel Casa Libertad, Mexico City 09620, DF, Mexico
Hernandez-Pineda, Jessica:
Secretaria Salud Mexico, Inst Nacl Perinatol, Dept Infectol & Inmunol, Mexico City 11000, DF, Mexico
Rodriguez-Bustamante, Eduardo:
Univ Nacl Autonoma Mexico, Inst Quim, Dept Quim Biomacromol, Mexico City 04510, DF, Mexico
Arreguin-Espinosa, Roberto:
Univ Nacl Autonoma Mexico, Inst Quim, Dept Quim Biomacromol, Mexico City 04510, DF, Mexico
Oria-Hernandez, Jesus:
Secretaria Salud Mexico, Inst Nacl Pediat, Lab Bioquim Genet, Mexico City 04530, DF, Mexico
Reyes-Vivas, Horacio:
Secretaria Salud Mexico, Inst Nacl Pediat, Lab Bioquim Genet, Mexico City 04530, DF, Mexico
Marcial-Quino, Jaime:
Secretaria Salud Mexico, Inst Nacl Pediat, Consejo Nacl Ciencia & Tecnol CONACYT, Mexico City 04530, DF, Mexico
Gomez-Manzo, Saul:
Secretaria Salud Mexico, Inst Nacl Pediat, Lab Bioquim Genet, Mexico City 04530, DF, Mexico
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