Glutaryl-CoA Dehydrogenase Misfolding in Glutaric Acidemia Type 1.

ABSTRACT: Glutaric acidemia type 1 (GA1) is a neurotoxic metabolic disorder due to glutaryl-CoA dehydrogenase (GCDH) deficiency. The high number of missense variants associated with the disease and their impact on GCDH activity suggest that disturbed protein conformation can affect the biochemical phenotype. We aimed to elucidate the molecular basis of protein loss of function in GA1 by performing a parallel analysis in a large panel of GCDH missense variants using different biochemical and biophysical methodologies. Thirteen GCDH variants were investigated in regard to protein stability, hydrophobicity, oligomerization, aggregation, and activity. An altered oligomerization, loss of protein stability and solubility, as well as an augmented susceptibility to aggregation were observed. GA1 vari

SUBMITTER: Barroso M 

PROVIDER: S-EPMC10487539 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature