| Autor: |
Louis, Naveen Eugene, Hamza, Muaawia Ahmed, Engku Baharuddin, Puteri Nur Sarah Diana, Chandran, Shamini, Latif, Nurriza Ab, Alonazi, Mona Awad, Jamalis, Joazaizulfazli, Warsy, Arjumand, Amran, Syazwani Itri |
| Předmět: |
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| Zdroj: |
Molecular Simulation; Jan2024, Vol. 50 Issue 1, p63-74, 12p |
| Abstrakt: |
Glucose-6-phosphate-dehydrogenase deficiency is the most common enzymopathy. Current therapies for G6PD deficiency are unable to treat a broad range of pathogenic variants. In this study, we assess the structural dynamics of six G6PD variants using molecular dynamics simulation to correlate their genotypic and phenotypic attributes. G6PD multimerisation is highly influenced by its ligands G6P and NADP, where the former disrupts dimer formation, and the latter facilitates tetramerisation. Results of our simulation demonstrate that the WT and a relatively stable variant (G131V), were found to have greater NADP binding occupancy and hydrogen bonds between βN sheet of each monomeric subunit, thereby increasing the stability of the dimer interface. G6PD protein structures with high structural integrity at the dimer interface were found to be compact, characterised by low radius of gyration values, and increased surface area or high solvent-accessible surface area at the tetramer salt bridge residues. Using mutational clustering methods, a critical G6PD region at the βK–βL loop was identified and may serve as a potential target for treatment. We further extend this study to identify chemical compounds that induce modulatory effects on the protein using computer aided drug discovery which warrant further studies and future testing. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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