A crucial active site network of titratable residues guides catalysis and NAD⁺ binding in human succinic semialdehyde dehydrogenase.

ABSTRACT: Human succinic semialdehyde dehydrogenase is a mitochondrial enzyme fundamental in the neurotransmitter γ-aminobutyric acid catabolism. It catalyzes the NAD⁺-dependent oxidative degradation of its derivative, succinic semialdehyde, to succinic acid. Mutations in its gene lead to an inherited neurometabolic rare disease, succinic semialdehyde dehydrogenase deficiency, characterized by mental and developmental delay. Due to the poor characterization of this enzyme, we carried out evolutionary and kinetic investigations to contribute to its functional behavior, a prerequisite to interpreting pathogenic variants. An in silico analysis shows that succinic semialdehyde dehydrogenases belong to two families, one human-like and the other of bacterial origin, differing in the oligomeric

SUBMITTER: Cesaro S 

PROVIDER: S-EPMC11681614 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature