PR00502

NUDIX hydrolase family

PRINTS entry
Member databasePRINTS
PRINTS typedomain
Short nameNUDIXFAMILY

Description

MutT is a small bacterial protein (~12-15Kd) involved in the GO system
[5]
responsible for removing an oxidatively damaged form of guanine (8-hydroxy-guanine or 7,8-dihydro-8-oxoguanine) from the nucleotide pool. 8-oxo-dGTP is inserted opposite dA and dC residues of template DNA with near equal efficiency, leading to A.T to G.C transversions. MutT degrades 8-oxo-dGTP to the monophosphate, with the concomitant release of pyrophosphate. A short conserved N-terminal region of mutT (designated the MutT domain) is also found in a variety of other prokaryotic, viral, and eukaryotic proteins
[2, 6, 3, 1]
.

Recently, the generic name 'NUDIX hydrolases' (NUcleoside DIphosphate linke to some other moeity X) has been coined for this domain family
[4]
. The family can be divided into a number of subgroups, of which MutT anti-mutagenic activity represents only one type; most of the rest hydrolyse diverse nucleoside diphosphate derivatives (including ADP-ribose, GDP-mannose, TDP-glucose, NADH, UDP-sugars, dNTP and NTP).

NUDIXFAMILY is a 2-element fingerprint that provides a signature for the NUDIX hydrolase family. The fingerprint was derived from an initial alignment of 12 sequences - the motifs span the full length of the MutT domain, and include the region encoded by PROSITE pattern MUTT (PS00893), which contains 4 conserved Glu residues. Two iterations on OWL28.0 were required to reach convergence, at which point a true set comprising 47 sequences was identified.

An update on SPTR57_40f identified a true set of 4,241 sequences.

References

1.The MutT motif family of nucleotide phosphohydrolases in man and human pathogens (review). McLennan AG. Int. J. Mol. Med. 4, 79-89, (1999). PMID: 10373642

2.A highly conserved sequence motif defining the family of MutT-related proteins from eubacteria, eukaryotes and viruses. Koonin EV. Nucleic Acids Res. 21, 4847, (1993). View articlePMID: 8233837

3.Cloning and expression of cDNA for a human enzyme that hydrolyzes 8-oxo-dGTP, a mutagenic substrate for DNA synthesis. Sakumi K, Furuichi M, Tsuzuki T, Kakuma T, Kawabata S, Maki H, Sekiguchi M. J. Biol. Chem. 268, 23524-30, (1993). View articlePMID: 8226881

4.The MutT proteins or "Nudix" hydrolases, a family of versatile, widely distributed, "housecleaning" enzymes. Bessman MJ, Frick DN, O'Handley SF. J. Biol. Chem. 271, 25059-62, (1996). View articlePMID: 8810257

5.The GO system protects organisms from the mutagenic effect of the spontaneous lesion 8-hydroxyguanine (7,8-dihydro-8-oxoguanine). Michaels ML, Miller JH. J. Bacteriol. 174, 6321-5, (1992). View articlePMID: 1328155

6.Characterization of the mutX gene of Streptococcus pneumoniae as a homologue of Escherichia coli mutT, and tentative definition of a catalytic domain of the dGTP pyrophosphohydrolases. Mejean V, Salles C, Bullions LC, Bessman MJ, Claverys JP. Mol. Microbiol. 11, 323-30, (1994). View articlePMID: 8170394

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