Next Article in Journal
Molecular Dynamics Simulations and Dynamic Network Analysis Reveal the Allosteric Unbinding of Monobody to H-Ras Triggered by R135K Mutation
Previous Article in Journal
Impaired Sleep, Circadian Rhythms and Neurogenesis in Diet-Induced Premature Aging
Article Menu
Issue 11 (November) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2017, 18(11), 2244; https://doi.org/10.3390/ijms18112244

Biochemical Analysis of Two Single Mutants that Give Rise to a Polymorphic G6PD A-Double Mutant

1
Laboratorio de Bioquímica Genética, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City 04530, Mexico
2
Laboratorio de Nutrición Experimental, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City 04530, Mexico
3
Consejo Nacional de Ciencia y Tecnología (CONACYT), Laboratorio de Agrobiotecnología, Tecnoparque CLQ, Universidad de Colima, Carretera los Limones-Loma de Juárez, Colima 28629, Mexico
4
Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico
5
Laboratorio de Neurociencias, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City 04530, Mexico
6
Laboratorio de Inmunoquímica, Hospital Infantil de México Federico Gómez, Secretaría de Salud, Mexico City 06720, Mexico
7
Colegio de Ciencias y Humanidades, Plantel Casa Libertad, Universidad Autónoma de la Ciudad de México, Mexico City 09620, Mexico
8
Departamento de Infectología e Inmunología, Instituto Nacional de Perinatología, Secretaría de Salud, Mexico City 11000, México
9
Departamento de Química de Biomacromoléculas, Instituto de Química, Universidad Nacional Autónoma de Mexico, Mexico City 04510, Mexico
10
Consejo Nacional de Ciencia y Tecnología (CONACYT), Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City 04530, Mexico
*
Authors to whom correspondence should be addressed.
Received: 10 September 2017 / Revised: 19 October 2017 / Accepted: 20 October 2017 / Published: 26 October 2017
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
View Full-Text   |   Download PDF [4021 KB, uploaded 26 October 2017]   |  

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. View Full-Text
Keywords: G6PD deficiency; kinetic parameters; thermal stability G6PD deficiency; kinetic parameters; thermal stability
Figures

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Ramírez-Nava, E.J.; Ortega-Cuellar, D.; Serrano-Posada, H.; González-Valdez, A.; Vanoye-Carlo, A.; Hernández-Ochoa, B.; Sierra-Palacios, E.; Hernández-Pineda, J.; Rodríguez-Bustamante, E.; Arreguin-Espinosa, R.; Oria-Hernández, J.; Reyes-Vivas, H.; Marcial-Quino, J.; Gómez-Manzo, S. Biochemical Analysis of Two Single Mutants that Give Rise to a Polymorphic G6PD A-Double Mutant. Int. J. Mol. Sci. 2017, 18, 2244.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top