Nudix

Nudix refers to a family of enzymes known as Nudix hydrolases, sometimes called MutT family proteins, named for a conserved Nudix motif within their sequence. The Nudix motif is a characteristic, roughly 23-residue sequence, written as GX5EX7REUXEEXGU, and it is located in the catalytic region of the enzyme. This motif coordinates metal ions and coordinates the chemical steps ofhydrolysis, making Nudix proteins highly dependent on divalent cations such as Mg2+ for activity.

Members of the Nudix family catalyze the hydrolysis of nucleoside diphosphate linked to X (NDP-X) substrates. They typically cleave a pyrophosphate bond to yield a monophosphate nucleotide (NMP) and a separate X moiety or phosphate group. Substrates are diverse and include oxidized nucleotides (such as 8-oxo-dGTP), diadenosine polyphosphates (ApnA), ADP-ribose, NADH, NAD+, and various cap structures on RNA. Through this chemistry, Nudix enzymes help sanitize the cellular nucleotide pool, regulate signaling molecules, and participate in RNA metabolism.

Distribution and examples extend across all domains of life. In bacteria, MutT is a well-known Nudix hydrolase that protects against oxidative DNA damage. In humans, several Nudix enzymes (for example NUDT1/MTH1, NUDT2, NUDT5, NUDT9, and NUDT15) participate in nucleotide pool maintenance, metabolism of signaling molecules, and, in some cases, drug metabolism and response. The Nudix family is defined primarily by its conserved motif and shared catalytic mechanism rather than a single substrate, reflecting a broad range of cellular roles.