A new view of missense mutations in α-mannosidosis using molecular dynamics conformational ensembles.

ABSTRACT: The mutation of remote positions on enzyme scaffolds and how these residue changes can affect enzyme catalysis is still far from being fully understood. One paradigmatic example is the group of lysosomal storage disorders, where the enzyme activity of a lysosomal enzyme is abolished or severely reduced. In this work, we analyze molecular dynamics simulation conformational ensembles to unveil the molecular features controlling the deleterious effects of the 43 reported missense mutations in the human lysosomal α-mannosidase. Using residue descriptors for protein dynamics, their coupling with the active site, and their impact on protein stability, we have assigned the contribution of each of the missense mutations into protein stability, protein dynamics, and their connectivity with the acti

SUBMITTER: Mandl S 

PROVIDER: S-EPMC11931667 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature