Biochemical Analysis of Two Single Mutants that Give Rise to a Polymorphic G6PD A-Double Mutant.
Int J Mol Sci
; 18(11)2017 Oct 26.
Article
em En
| MEDLINE
| ID: mdl-29072585
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Glucosefosfato Desidrogenase
/
Deficiência de Glucosefosfato Desidrogenase
/
Mutação
Limite:
Humans
Idioma:
En
Revista:
Int J Mol Sci
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
México