Original title: ASM Variants in the Spotlight: A Structure-Based Atlas for Unraveling Pathogenic Mechanisms in Lysosomal Acid Sphingomyelinase
Authors: Simone Scrima,Matteo Lambrughi,Matteo Tiberti,Elisa Fadda,Elena Papaleo
In this article, the author discusses the importance of lysosomal acid sphingomyelinase (ASM), an enzyme involved in lipid metabolism. Deficiencies in ASM can lead to a rare genetic disorder with various clinical manifestations. The author used a structure-based framework to analyze over 400 variants of ASM, combining pathogenicity predictions with molecular dynamics simulations. This comprehensive approach helped identify variants that affect the stability of the enzyme or have effects on its functional sites. To validate their predictions, the author compared them to experimental data on the enzyme’s activity. The study also suggests that the findings can be useful in identifying cases suitable for enzyme replacement therapy. Overall, the article enhances our understanding of ASM variants and provides insights for potential therapeutic interventions.
Original article: https://www.biorxiv.org/content/10.1101/2023.11.24.568551v2