ADP-ribosyltransferase-based biocatalysis of nonhydrolyzable NAD+ analogs.

ABSTRACT: Enzyme promiscuity is the ability of an enzyme to catalyze an unexpected side reaction in addition to its main reaction. Here, we describe a biocatalytic process to produce nonhydrolyzable NAD+ analogs based on the ADP-ribosyltransferase activity of pertussis toxin PtxS1 subunit. First, in identical manner to normal catalysis, PtxS1 activates NAD+ to form the reactive oxocarbenium cation. Subsequently, the electrophilic ribose 1' carbon of the oxocarbenium cation is subject of an attack by the nitrogen atom of an amino group coupled to nicotinamide mimicking compounds. The nitrogen atom acts as the nucleophile instead of the natural sulfur atom substrate of the human Gαi protein. The invention builds on structural data indicating the presence of an NAD+ analog, benzamide amino adenine dinu

SUBMITTER: Sakari M 

PROVIDER: S-EPMC11786771 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature