A cryptic activity in the Nudix hydrolase superfamily

Abstract

The Nudix hydrolase superfamily is identified by a conserved cassette of 23 amino acids, and it is characterized by its pyrophosphorylytic activity on a wide variety of nucleoside diphosphate derivatives. Of the 13 members of the family in Escherichia coli, only one, Orf180, has not been identified with a substrate, although a host of nucleoside diphosphate compounds has been tested. Several reports have noted a strong similarity in the three-dimensional structure of the unrelated enzyme, isopentenyl diphosphate isomerase (IDI) to the Nudix structure, and the report that a Nudix enzyme was involved in the synthesis of geraniol, a product of the two substrates of IDI, prompted an investigation of whether the IDI substrates, isopentenyl diphosphate (IPP), and dimethylallyl diphosphate (DAPP) could be substrates of Orf180. This article demonstrates that Orf180 does have a very low activity on IPP, DAPP, and geranyl pyrophosphate (GPP). However, several of the other Nudix enzymes with established nucleoside diphosphate substrates hydrolyze these compounds at substantial rates. In fact, some Nudix hydrolases have higher activities on IPP, DAPP, and GPP than on their signature nucleoside diphosphate derivatives.

Functional diversification in the Nudix hydrolase gene family drives sesquiterpene biosynthesis in Rosa × wichurana

“…Not so long ago, NUDX1 proteins were generally considered as ‘house cleaning’ enzymes (Bessman et al ., 1996; Yoshimura et al ., 2007; Bessman, 2019). Indeed, NUDX1 proteins from E. coli and humans have been shown to play major roles in removing oxidized nucleotides (Setoyama et al ., 2011; Gad et al ., 2014).…”

Clinical correlations and prognostic value of Nudix hydroxylase 10 in patients with gastric cancer

“…Nudix hydroxylases (NUDTs) are a family of Mg 2+ -requiring enzymes found in all classes of organisms that catalyze the hydrolysis of a wide range of nucleoside pyrophosphates linked to other moieties of amino acids [ 4 ]. All NUDTs consist of a Nudix hydroxylase fold and Nudix box, which is a conserved 23-residue sequence motif(GXXXXXEXXXXXXXREUXEEXGU, where U is a hydrophobic residue and X is any amino acid) [ 5 ].…”

Structural insight into molecular inhibitory mechanism of InsP6 on African Swine Fever Virus mRNA-decapping enzyme g5Rp

“…2 D ). The sequence of the g5Rp Nudix motif matches the classic pattern of the Nudix motif in the Nudix hydrolase superfamily; that is, GX5EX7REUXEEXGU, where X is any residue and U is Ile, Leu, or Val 29,30 . Using the Dali server 31 , we compared the structure of the g5Rp with that of other proteins in the Protein Data Bank (PDB), whereupon 46 structures were found to be likely homologous to the enzyme, with Z-scores in the range of 8–20 (Supplementary, Table 2).…”