Molecular and Cellular Studies Reveal Folding Defects of Human Ornithine Aminotransferase Variants Associated With Gyrate Atrophy of the Choroid and Retina.

ABSTRACT: The deficit of human ornithine aminotransferase (hOAT) is responsible for gyrate atrophy (GA), a rare recessive inherited disorder. Although more than 60 disease-associated mutations have been identified to date, the molecular mechanisms explaining how each mutation leads to the deficit of OAT are mostly unknown. To fill this gap, we considered six representative missense mutations present in homozygous patients concerning residues spread over the hOAT structure. E. coli expression, spectroscopic, kinetic and bioinformatic analyses, reveal that the R154L and G237D mutations induce a catalytic more than a folding defect, the Q90E and R271K mutations mainly impact folding efficiency, while the E318K and C394Y mutations give rise to both folding and catalytic defects. In a human cellul

SUBMITTER: Montioli R 

PROVIDER: S-EPMC8360850 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature