Molecular Characterization of the GALC Mutation Thr112Ala Causing Krabbe Disease.

ABSTRACT: Krabbe disease is a rare and severe lysosomal disorder affecting the white matter of the central and peripheral nervous system. It is characterized by neurodegeneration, with the most common form being infantile Krabbe disease, typically diagnosed within the first year of life. This autosomal-recessive disease is caused by mutations in the GALC gene, which encodes the lysosomal enzyme β-galactocerebrosidase. This study focuses on a β-galactocerebrosidase variant, with Thr112Ala identified as a homozygous mutation in a patient with infantile Krabbe disease. To understand the structural effects of this mutation, we conducted all-atom molecular dynamics simulations of both the mutant and wild-type (wt) enzymes at cytosolic (pH 7.0) and lysosomal pH (pH 4.5), as β-galactocerebrosidase i

SUBMITTER: Heger L 

PROVIDER: S-EPMC12429000 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature