Structural insights into mutated human phosphoglucomutase 1 (PGM1) using computational approaches.

The phosphoglucomutase 1 (PGM1) enzyme plays a critical role in metabolism and glycosylation in the human body. PGM1 has been linked to multiple disease phenotypes, including the inherited metabolic disorder known as congenital disorders of glycosylation (CDGs). Numerous clinical studies have shown that mutations in key regions of the PGM1 gene affect catalytic activity and induce folding defects of the enzyme. To delve into molecular changes at the supramolecular level, the structural, stability, and other features of PGM1 variants (T19A, N38Y, and D62H) were studied in the present work. To this end, molecular dynamics (MD) simulation at a long timescale (500 ns) was carried out. Parameters such as root-mean-square deviation (RMSD), root-mean-square fluctuations (RMSF), radius of gyration (Rg), solvent-accessible surface area (SASA), hydrogen bonds, and free energy landscape (FEL) were studied and compared with those of the wild-type PGM1. It was noted that mutations 19 A, N38Y, and D62H significantly alter the protein's structural behavior, causing increased flexibility, reduced stability, and compactness.