Effects of Single and Double Mutants in Human Glucose-6-Phosphate Dehydrogenase Variants Present in the Mexican Population: Biochemical and Structural Analysis
Year: 2020
Type: article
Abstract: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most frequent human enzymopathy, affecting over 400 million people globally. Worldwide, 217 mutations have been reported at the genetic level, and only 19 have been found in Mexico. The objective of this work was to contribute to the knowledge of the function and structure of three single natural variants (G6PD A+, G6PD San Luis Potosi, and G6PD Guadalajara) and a double mutant (G6PD Mount Sinai), each localized in a different region of the three-dimensional (3D) structure. In the functional characterization of the mutants, we observed a decrease in specific activity, protein expression and purification, catalytic efficiency, and substrate affinity in comparison with wild-type (WT) G6PD. Moreover, the analysis of the effect of all mutations on the structural stability showed that its presence increases denaturation and lability with temperature and it is more sensible to trypsin digestion protease and guanidine hydrochloride compared with WT G6PD. This could be explained by accelerated degradation of the variant enzymes due to reduced stability of the protein, as is shown in patients with G6PD deficiency.
DOI: 10.3390/ijms21082732
Authors: Víctor Martínez-Rosas, Merit Juárez-Cruz, Edson Ramírez-Nava, Beatriz Hernández-Ochoa, Laura Morales-Luna, Abigail González-Valdez, Hugo Serrano-Posada, Noemí Cárdenas-Rodríguez, Paulina Ortiz-Ramírez, Sara Centeno-Leija, Roberto Arreguin-Espinosa, Miguel Cuevas-Cruz, Daniel Ortega-Cuellar, Verónica Pérez de la Cruz, Luz Rocha-Ramírez, Edgar Sierra-Palacios, Rosa Castillo-Rodríguez, Isabel Baeza-Ramírez, Jaime Marcial-Quino, Saúl Gómez-Manzo
Institutions: Secretaria de Salud, Instituto Nacional de Pediatria, Instituto Politécnico Nacional, Universidad Nacional Autónoma de México, Hospital Infantil de México Federico Gómez, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Secretaría de Ciencia, Humanidades, Tecnología e Innovación, Universidad de Colima, Instituto Nacional de Neurología y Neurocirugía, Universidad Autónoma de la Ciudad de México
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,112
Awards: G1498598460, G4763834835, G6177323053
OpenAlex ID: W3016668097