Biochemical Analysis of Two Single Mutants that Give Rise to a Polymorphic G6PD A-Double Mutant
2017
Edson Jiovany Ramírez-Nava | Daniel Ortega-Cuellar | Hugo Serrano-Posada | Abigail González-Valdez | America Vanoye-Carlo | Beatriz Hernández-Ochoa | Edgar Sierra-Palacios | Jessica Hernández-Pineda | Eduardo Rodríguez-Bustamante | Roberto Arreguin-Espinosa | Jesús Oria-Hernández | Horacio Reyes-Vivas | Jaime Marcial-Quino | Saúl Gómez-Manzo
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.
اظهر المزيد [+] اقل [-]الكلمات المفتاحية الخاصة بالمكنز الزراعي (أجروفوك)
المعلومات البيبليوغرافية
تم تزويد هذا السجل من قبل Directory of Open Access Journals
