Structural insights into the pathogenicity of point mutations in human acyl-CoA dehydrogenase homotetramers.

ABSTRACT: Acyl-CoA dehydrogenase deficiency (ACAD) is an inherited and potentially fatal disorder with variable clinical symptoms. The relationship between pathogenicity and deleterious point mutations is investigated here in ACAD structures of short (SCAD) and medium-chain (MCAD) types. Structures and dynamic features of native and mutant forms of enzymes models were compared. A total of 2.88 µs molecular dynamics simulations were performed at four different temperatures. Total energy, RMSD, protein ligand interactions and affinity, RMSF measures, secondary structure changes, and important interactions were studied. Mutations in the three main domains of ACADs are pathogenic, while those located at linker turns are not. Mutations affect mostly tetramer formations, secondary structures, and many con

SUBMITTER: Faraji H 

PROVIDER: S-EPMC10864237 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature