Comparative study of structural changes caused by different substitutions at the same residue on α-galactosidase A.

ABSTRACT: Missense mutations in the α-galactosidase A (GLA) gene comprising the majority of mutations responsible for Fabry disease result in heterogeneous phenotypes ranging from the early onset severe "classic" form to the "later-onset" milder form. To elucidate the molecular basis of Fabry disease from the viewpoint of structural biology, we comprehensively examined the effects of different substitutions at the same residue in the amino acid sequence of GLA on the structural change in the enzyme molecule and the clinical phenotype by calculating the number of atoms affected and the root-mean-square-distance value, and by coloring of the atoms influenced by the amino acid replacements. The results revealed that the severity of the structural change influences the disease progression, i.e., a small

SUBMITTER: Saito S 

PROVIDER: S-EPMC3873411 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature