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

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.

Site-Selective Protein Conjugation by a Multicomponent Ugi Reaction.

The chemical bioconjugation of proteins has seen tremendous applications in the past decades, with the booming of antibody-drug conjugates and their use in oncology. While genetic engineering has permitted to produce bespoke proteins featuring key (un-)natural amino acid residues poised for site-selective modifications, the conjugation of native proteins is riddled with selectivity issues. Chemoselective strategies are plentiful and enable the precise modification of virtually any residue with a reactive side-chain; site-selective methods are less common and usually most effective on small and medium-sized proteins.

Compound heterozygosis in AADC deficiency: A complex phenotype dissected through comparison among heterodimeric and homodimeric AADC proteins.

Compound heterozygosis is the most diffuse and hardly to tackle condition in aromatic amino acid decarboxylase (AADC) deficiency, a genetic disease leading to severe neurological impairment. Here, by using an appropriate vector, we succeeded in obtaining high yields of AADC protein and characterizing two new heterodimers, T69M/S147R and C281W/M362T, detected in two AADC deficiency patients. We performed an extensive biochemical characterization of the heterodimeric recombinant proteins and of the related homodimers, by a combination of dichroic and fluorescence spectroscopy and activity assays together with bioinformatic analyses.

Oxygen reactivity with pyridoxal 5'-phosphate enzymes: biochemical implications and functional relevance.

The versatility of reactions catalyzed by pyridoxal 5'-phosphate (PLP) enzymes is largely due to the chemistry of their extraordinary catalyst. PLP is necessary for many reactions involving amino acids. Reaction specificity is controlled by the orientation of the external aldimine intermediate that is formed upon addition of the amino acidic substrate to the coenzyme.