Preliminary study of structural changes of Glucose-6-phosphate dehydrogenase deficiency variants

• Main Authors: Louis, Naveen E., Hamza, Muaawia A., Engku Baharuddin, Puteri N. S. D., Chandran, Shamini, A. Latif, Nurriza, Alonazi, Mona A., Halim, Khairul B. A., Warsy, Arjumand, Amran, Syazwani I.
• Format: Article
• Language: English
• Published: China Medical University 2022
• Subjects: QD Chemistry
• Online Access: http://eprints.utm.my/id/eprint/101238/1/NurrizaAbLatif2022_PreliminaryStudyofStructuralChangesofGlucose6Phosphate.pdf; http://eprints.utm.my/id/eprint/101238/; http://dx.doi.org/10.37796/2211-8039.1355

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme deficiency disorder affecting over 400 million individuals worldwide. G6PD protects red blood cells (RBC) from the harmful effects of oxidative substances. There are more than 400 G6PD mutations, of which 186 variants have shown to be linked to G6PD deficiency by decreasing the activity or stability of the enzyme. Different variants manifest different clinical phenotypes which complicate comprehending the mechanism of the disease. In order to carry out computational approaches to elucidate the structural changes of different G6PD variants that are common to the Asian population, a complete G6PD monomer-ligand complex was constructed using AutoDock 4.2, and the molecular dynamics simulation package GROMACS 4.6.7 was used to study the protein dynamics. The G410D and V291M variants were chosen to represent classes I and II respectively and were created by in silico site-directed mutagenesis. Results from the Root mean square deviation (RMSD), Root mean square fluctuation (RMSF) and Radius of gyration (Rg) analyses provided insights on the structure - function relationship for the variants. G410D indicated impaired dimerization and structural NADP binding while the impaired catalytic activity for V291M was indicated by a conformational change at its mutation site.