PMC:101403 / 1509-4671 JSONTXT

{"project":"2_test","denotations":[{"id":"11943069-8810257-8112308","span":{"begin":325,"end":326},"obj":"8810257"},{"id":"11943069-10373642-8112309","span":{"begin":327,"end":328},"obj":"10373642"},{"id":"11943069-8810257-8112310","span":{"begin":523,"end":524},"obj":"8810257"},{"id":"11943069-8233837-8112311","span":{"begin":525,"end":526},"obj":"8233837"},{"id":"11943069-7569993-8112312","span":{"begin":857,"end":858},"obj":"7569993"},{"id":"11943069-11145417-8112313","span":{"begin":893,"end":894},"obj":"11145417"},{"id":"11943069-11136450-8112314","span":{"begin":895,"end":896},"obj":"11136450"},{"id":"11943069-10873676-8112315","span":{"begin":1812,"end":1813},"obj":"10873676"},{"id":"11943069-10567213-8112316","span":{"begin":1915,"end":1916},"obj":"10567213"},{"id":"11943069-11825615-8112317","span":{"begin":1967,"end":1969},"obj":"11825615"},{"id":"11943069-10777568-8112318","span":{"begin":2049,"end":2051},"obj":"10777568"},{"id":"11943069-11415433-8112319","span":{"begin":2163,"end":2165},"obj":"11415433"},{"id":"11943069-10205176-8112320","span":{"begin":2294,"end":2296},"obj":"10205176"},{"id":"11943069-10508173-8112321","span":{"begin":2297,"end":2299},"obj":"10508173"},{"id":"11943069-1766361-8112322","span":{"begin":2373,"end":2375},"obj":"1766361"},{"id":"11943069-11361135-8112323","span":{"begin":2452,"end":2454},"obj":"11361135"},{"id":"11943069-10922370-8112324","span":{"begin":2455,"end":2457},"obj":"10922370"},{"id":"11943069-11415433-8112325","span":{"begin":2498,"end":2500},"obj":"11415433"}],"text":"Background\nThe Nudix hydrolase family comprises enzymes that hydrolyse predominantly the diphosphate (pyrophosphate) linkage in a variety of nucleoside triphosphates, dinucleoside polyphosphates, nucleotide sugars and nucleotide cofactors having the general structure of a nucleoside diphosphate linked to another moiety, X [1,2]. They are found in archaea, eubacteria, animal, plants, and fungi and all possess the Nudix box sequence signature motif Gx5Ex5 [UA]xREx2EExGU (where U is an aliphatic hydrophobic amino acid) [1,3]. The proposed functions of this family are to eliminate potentially toxic nucleotide metabolites from the cell and to regulate the concentrations of nucleotide cofactors and signalling molecules for optimal cell growth and survival.\nThe number of genes encoding Nudix hydrolases varies widely, from zero in Mycoplasma genitalium[4] to 22 in Deinococcus radiodurans[5,6]. This variation presumably reflects the growth or environmental adaptability, stress tolerance and metabolic capacity of the different organisms. The Nudix hydrolases thus offer an ideal system with which to study the evolution of a largely inessential protein family and its contribution to the individual biology of an organism. Understanding such variation requires a combination of detailed biochemical, genetic and cellular studies to reveal the individual functions of family members within the set in any given system. In the case of multicellular eukaryotes, the nematode Caenorhabditis elegans offers a genetically amenable model system with which to carry out such studies. There are 11 members of the Nudix hydrolase family in C. elegans. So far only two of these have been characterized – a diadenosine tetraphosphate pyrophosphohydrolase (the orthologue of human NUDT2) [7] and an NADH diphosphatase [8]. Sequence comparisons would predict the existence of an ADP-sugar diphosphatase (NUDT5 orthologue) [9], an ADP-ribose diphosphatase (NUDT9 orthologue) [10], a diphosphoinositol polyphosphate pyrophosphohydrolase (NUDT3/4 orthologue) [11], two probable coenzyme A diphosphatases, one of which is highly similar to the mouse Nudt7 CoA diphosphatase [12], and 4 proteins of unknown function, including one with a strong similarity to the Saccharomyces cerevisiae PSU1/DCP2 protein [13,14] and another similar to the developmentally-regulated mouse RP2 protein [15].\nRecent characterization of the S. cerevisiae NADH and CoA diphosphatases [16,17] and the mouse Nudt7 CoA diphosphatase [12] has revealed that they are located in peroxisomes. The function of these peroxisomal enzymes may be to regulate the concentration of these essential nucleotide cofactors for peroxisomal metabolism or, by analogy with the E. coli MutT 8-oxo-dGTPase, to eliminate toxic modified cofactor metabolites from the highly oxidizing peroxisomal environment. In order to investigate these possibilities in the C. elegans model system, we have cloned and characterised the putative C. elegans Y87G2A.14 CoA diphosphatase and shown that it displays the expected enzymatic activities and that it appears to be targetted to peroxisomes by a C-terminal PTS1 targeting signal."}