The Nudix superfamily is widespread among eucaryotes, bacteria, archaea and
viruses and consists mainly of pyrophosphohydrolases that act upon substrates
of general structure NUcleoside DIphosphate linked to another moiety, X
(NDP-X) to yield NMP plus P-X. Such substrates include (d)NTPs (both canonical
and oxidised derivatives), nucleotide sugars and alcohols, dinucleoside
polyphosphates (NpnN), dinucleotide coenzymes and capped RNAs. However,
phosphohydrolase activity, including activity towards NDPs themselves, and
non-nucleotide substrates such as diphosphoinositol polyphosphates (DIPs),
5-phosphoribosyl 1-pyrophosphate (PRPP), thiamine pyrophosphate (TPP) and
dihydroneopterin triphosphate (DHNTP) have also been described. Some
superfamily members, such as Escherichia coli mutT, have the ability to
degrade potentially mutagenic, oxidised nucleotides while others control the
levels of metabolic intermediates and signalling compounds. In procaryotes and
simple eucaryotes, the number of Nudix genes varies from 0 to over 30,
reflecting the metabolic complexity and adaptability of the organism. Nudix
hydrolases are typically small proteins, larger ones having additional domains
with interactive or other catalytic functions
[4].
The Nudix domain formed by two beta-sheets packed between alpha-helices
[2][3]. It can accomodate sequences of different lengths in the
connecting loops and in the amtiparallel beta-sheet. Catalysis depends on the
conserved 23-amino acid Nudix motif (Nudix box), G-x(5)-E-x(5)-[UA]-x-R-E-
x(2)-E-E-x-G-U, where U is an aliphatic, hydrophobic residue. This sequence is
located in a loop-helix-loop structural motif and the Glu residues in the core
of the motif, R-E-x(2)-E-E, play an important role in binding essential
divalent cations
[4]. The substrate specificity is determined by other
residues outside the Nudix box. For example, CoA pyrophosphatases share the
NuCoA motif L-L-T-x-R-[SA]-x(3)-R-x(3)-G-x(3)-F-P-G-G that is located N-
terminal of the Nudix box and is involved in CoA recognition
[1].
Some proteins known to contain a Nudix domain are listed below:
- Bacterial mutator mutT protein (7,8-dihydro-8-oxoguanine-triphosphatase)
(8-oxo-dGTPase) (3.6.1.-) (dGTP pyrophosphohydrolase).
- Streptomyces pneumoniae mutX.
- Escherichia coli nudB (ntpA) dihydroneopterin triphosphate pyrophosphatase
(EC 3.6.1.-) (dATP pyrophosphohydrolase).
- Escherichia coli (yjaD) and Haemophilus influenzae (HI0432) nudC NADH
pyrophosphatase (EC 3.6.1.22).
- Escherichia coli nudE (yrfE) ADP compounds hydrolase (EC 3.6.1.-).
- Bacterial nudH (rppH) RNA pyrophosphohydrolase (EC 3.6.1.-) ((Di)nucleoside
polyphosphate hydrolase).
- Escherichia coli nudI (yfaO) nucleoside triphosphatase (EC 3.6.1.-).
- Escherichia coli uncharacterized Nudix hydrolase nudL (EC 3.6.1.-).
- Streptomyces ambofaciens MutT-like protein from plasmid pSAM2.
- Bacillus subtilis hypothetical protein yqkG.
- Bacillus subtilis hypothetical protein yzgD.
- Mammalian NUDT1 and NUDT15 7,8-dihydro-8-oxoguanine triphosphatase
(EC 3.1.6.-).
- Mammalian NUDT2 diadenosine 5',5'''-P1,P4-tetraphosphate asymmetrical
hydrolase (Ap4Aase) (EC 3.6.1.17) [5], which cleaves A-5'-PPPP-5'A to yield
AMP and ATP.
- Higher vertebrates NUDT6 nucleoside diphosphate-linked moiety X motif 6, a
protein encoded on the antisense RNA of the basic fibroblast growth factor
gene.
- Yeast ADP-ribose pyrophosphatase (EC 3.6.1.13) (YSA1).
- Yeast NADH pyrophosphatase (EC 3.6.1.22) (NPY1) (YGL067W).
- Yeast peroxisomal coenzyme A diphosphatase 1, peroxisomal (EC 3.6.1.-)
(PCD1).
- African swine fever viruses protein D250.
- Poxviruses proteins D9 and D10.
We developed two patterns for the Nudix domain. The first one covers the Nudix
box and the second the NuCoA motif. We also developed a profile which covers
the entire Nudix domain.