In Saccharomyces cerevisiae, lithium induces a ‘galactosemia-like’ phenotype as a consequence of inhibition of phosphoglucomutase, a key enzyme in galactose metabolism. Figure The role of Thr28 and a water molecule in the local unfolding process around the point mutation of human galactokinase Based on the results, we propose a possible mechanism for the unfolding caused by the Pro28Thr point mutation. Local unfolding was verified by several other MD simulations performed with different duration, initial velocities and force field. Another consequence was the decrease in stability (5–7 kcal mol−1) around this region, as confirmed by ΔGbind calculations for the extracted part of the whole system. Altered H-bonding networks were detected based on geometric and electron density criteria that resulted in local unfolding of the β-sheet secondary structure. This paper reports a study of the Pro28Thr point mutation using a variety of theories including molecular dynamics (MD), MM-PBSA/GBSA calculations and AIM analysis. Malfunctioning of galactokinase due to a single point mutation causes cataracts and, in serious cases, blindness. Galactokinase is responsible for the phosphorylation of α-d-galactose, which is an important step in the metabolism of the latter.
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