Conformational Dynamics of Mitochondrial Inorganic Pyrophosphatase hPPA2 and Its Changes Caused by Pathogenic Mutations.

ABSTRACT: Inorganic pyrophosphatases, or PPases, are ubiquitous enzymes whose activity is necessary for a large number of biosynthetic reactions. The catalytic function of PPases is dependent on certain conformational changes that have been previously characterized based on the comparison of the crystal structures of various complexes. The current work describes the conformational dynamics of a structural model of human mitochondrial pyrophosphatase hPPA2 using molecular dynamics simulation, all-atom principal component analysis, and coarse-grained normal mode analysis. In addition to the wild-type enzyme, four mutant variants of hPPA2 were characterized that correspond to the natural pathogenic variants causing severe mitochondrial dysfunction and cardio pathologies. As a result, we identified the

SUBMITTER: Bezpalaya E 

PROVIDER: S-EPMC11766831 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature