The Nudix hydrolase superfamily

Abstract

Nudix hydrolases are found in all classes of organism and hydrolyse a wide range of organic pyrophosphates, including nucleoside di- and triphosphates, dinucleoside and diphosphoinositol polyphosphates, nucleotide sugars and RNA caps, with varying degrees of substrate specificity. Some superfamily members, such as Escherichia coli MicrotT, have the ability to degrade potentially mutagenic, oxidised nucleotides while others control the levels of metabolic intermediates and signalling compounds. In prokaryotes and simple eukaryo tes, the number of Nudix genes varies from 0 to over 30, reflecting the metabolic complexity and adaptability of the organism. Mammals have around 24 Nudix genes, several of which encode more than one variant. This review integrates the sizeable recent literature on these proteins with information from global functional genomic studies to provide some insights into the possible roles of different superfamily members in cellular metabolism and homeostasis and to stimulate discussion and further research into this ubiquitous protein family.

Actinomycete integrative and conjugative pMEA-like elements of Amycolatopsis and Saccharopolyspora decoded

“…A well-known Nudix protein is MutT of E. coli, which degrades potentially mutagenic nucleotides. Other Nudix proteins control the levels of metabolic intermediates and signalling compounds (McLennan, 2006). The pif gene of pSAM2 encodes a Nudix hydrolase (Pif) that confers conjugal immunity.…”

Structural basis of UGUA recognition by the Nudix protein CFI m 25 and implications for a regulatory role in mRNA 3′ processing

“…The large subunit, encoded by either of two paralogs (CPSF6 and CPSF7), contains an N-terminal RNA Recognition Motif (RRM), an internal polyproline-rich region, and a C-terminal RS/RD alternating charge domain-a structure similar to that of the SR-protein family of splicing regulators. The small subunit (CFI m 25) contains a Nudix domain, a protein domain that most often participates in the hydrolysis of substrates containing a nucleotide diphosphate linked to a variable moiety X (15). Found throughout all three kingdoms, Nudix proteins participate in a wide range of crucial housekeeping functions, including the hydrolysis of mutagenic nucleotides, the modulation of the levels of signaling molecules, and the monitoring of metabolic intermediates (15).…”

Effects of 8-hydroxy-GTP and 2-hydroxy-ATP on in vitro transcription

“…The importance of oxidized DNA precursors is highlighted by the presence of Escherichia coli MutT and its functional homologues, and by the phenotypes of mutant organisms lacking the MutT-type enzymes [ref. 4 and references therein]. The direct introduction of oxidized DNA precursors into living cells induces mutations in chromosomal genes, providing another line of evidence that they are mutagens when produced in cells [5,6].…”

“…The findings that some MutT-type enzymes including human MTH1 protein catalyze the hydrolysis of oxidized RNA precursors suggest the importance of the hydrolytic elimination of oxidized ribonucleotides [ref. 4 and references therein]. Moreover, the yeast S-II null mutant exhibits sensitivity to oxidants and is defective in maintaining transcriptional fidelity [14].…”