Dimeric dUTPases, HisE, and MazG belong to a New Superfamily of all-α NTP Pyrophosphohydrolases with Potential “House-cleaning” Functions

Moroz, Olga V.; Murzin, Alexey G.; Makarova, Kira S.; Koonin, Eugene V.; Wilson, K.S.; Galperin, Michael Y.

doi:10.1016/j.jmb.2005.01.030

Cited by 79 publications

(111 citation statements)

References 70 publications

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“…The first 3D structure of a MazG enzyme from Sulfolobus solfataricus (PDB code: 1VMG) enabled its classification into the newly-identified all-a NTP PPase superfamily by sequence-and structure-based comparisons [92]. The cognate ligand, found with poor resolution at the active sites of the tetramer structure was identified as 2-oxo dATP.…”

Section: Mazgmentioning

confidence: 99%

Preventive DNA repair by sanitizing the cellular (deoxy)nucleoside triphosphate pool

2014

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The occurrence of modified bases in DNA is attributed to some major factors: incorporation of altered nucleotide building blocks and chemical reactions or radiation effects on bases within the DNA structure. Several enzyme families are involved in preventing the incorporation of noncanonical bases playing a 'sanitizing' role. The catalytic mechanism of action of these enzymes has been revealed for a number of representatives in clear structural and kinetic detail. In this review, we focus in detail on those examples where clear evidence has been produced using high-resolution structural studies. Comparing the protein fold and architecture of the enzyme active sites, two main classes of sanitizing deoxyribonucleoside triphosphate pyrophosphatases can be assigned that are distinguished by the site of nucleophilic attack. In enzymes associated with attack at the a-phosphorus, it is shown that coordination of the c-phosphate group is also ensured by multiple interactions. By contrast, enzymes catalyzing attack at the b-phosphorus atom mainly coordinate the a-and the b-phosphate only. Characteristic differences are also observed with respect to the role of the metal ion cofactor (Mg 2+ ) and the coordination of nucleophilic water. Using different catalytic mechanisms embedded in different protein folds, these enzymes present a clear example of convergent evolution.

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Section: Mazgmentioning

confidence: 99%

Preventive DNA repair by sanitizing the cellular (deoxy)nucleoside triphosphate pool

2014

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“…The other notable prediction in this cluster is attributed to ORF 67, which encodes a probable nucleoside triphosphate pyrophosphohydrolase enzyme. Pyrophosphohydrolase activity is necessary in catalysing the removal of pyrophosphates resulting from nucleoside triphosphates (NTPs) hydrolysis (Moroz et al, 2005). Furthermore, NTP-pyrophosphohydrolase activity is reported to have a role in cellular stress responses and 'house-cleaning' functions (Lu et al, 2010;Moroz et al, 2005).…”

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confidence: 99%

Genomic and phenotypic characterization of Rhizobium gallicum phage vB_RglS_P106B

et al. 2015

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The phage P106B (vB_RglS_P106B) is a Siphoviridae phage with a narrow spectrum of infectivity, which has been isolated from soils with a history of pea cultivation. The trapping host of P106B is an indigenous strain of Rhizobium gallicum (SO14B-4) isolated from soils associated with Vicia cracca. Phenotypic characterization of the phage revealed that P106B has an approximate burst size of 21 p.f.u. per infected cell with 60 min and 100 min eclipse and latent periods, respectively. Phage P106B was unable to transduce under the conditions tested. The genome of P106B is 56 024 bp in length with a mean DNA G+C content of 47.9 %. The complete genome sequence contains 95 putative ORFs and a single tRNA gene coding for leucine with the anticodon TTA. Putative functions could only be assigned to 22 of the predicted ORFs while a significant number of ORFs (47) shared no sequence similarities to previously characterized proteins. The remaining 26 putative protein-coding genes exhibited a sequence resemblance to other hypothetical proteins. No lysogeny-related genes were found in the P106B genome.

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“…Through sequence analysis restricted to the active site motif, Moroz et al (6,7) identified a "basic module" of the dUTPase/ dCTPase family in the genomes of several Gram-positive bacteria and respective phages. This basic module, consisting of only five active site-forming helices, is conserved in two other families: the nonspecific NTP-PPase MazG and phosphoribosyl-ATP pyrophosphatase HisE.…”

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confidence: 99%

“…These three enzyme families, which share similar function, were unified into a single superfamily, the all-␣-NTP-PPase superfamily. Following the same criteria, DR2231 was identified by sequence analysis as a putative member of this superfamily, as were two other genes encoding MazG family proteins, DR1022 and DR1183 (7). We performed a broader sequence search using as a query the sequence of Escherichia coli MazG protein, (8) against the D. radiodurans genome and identified only DR1022 and DR1183 as MazG-like proteins.…”

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confidence: 99%

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Structural and Functional Insights into DR2231 Protein, the MazG-like Nucleoside Triphosphate Pyrophosphohydrolase from Deinococcus radiodurans

Gonçalves¹,

Sanctis

McSweeney

2011

Journal of Biological Chemistry

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Deinococcus radiodurans is among the very few bacterial species extremely resistant to ionizing radiation, UV light, oxidizing agents, and cycles of prolonged desiccation. The proteome of D. radiodurans reflects the evolutionary pressure exerted by chronic exposure to (nonradioactive) forms of DNA and protein damage. A clear example of this adaptation is the overrepresentation of protein families involved in the removal of non-canonical nucleoside triphosphates (NTPs) whose incorporation into nascent DNA would promote mutagenesis and DNA damage. The three-dimensional structure of the DR2231 protein has been solved at 1.80 Å resolution. This protein had been classified as an all-␣-helical MazG-like protein. The present study confirms that it holds the basic structural module characteristic of the MazG superfamily; two helices form a rigid domain, and two helices form a mobile domain and connecting loops. Contrary to what is known of MazG proteins, DR2231 protein shows a functional affinity with dUTPases. Enzymatic and isothermal calorimetry assays have demonstrated high specificity toward dUTP but an inability to hydrolyze dTTP, a typical feature of dUTPases. Co-crystallization with the product of hydrolysis, dUMP, in the presence of magnesium or manganese cations, suggests similarities with the dUTP/dUDP hydrolysis mechanism reported for dimeric dUTPases. The genome of D. radiodurans encodes for all enzymes required for dTTP synthesis from dCMP, thus bypassing the need of a dUTPase. We postulate that DR2231 protein is not essential to D. radiodurans and rather performs "house-cleaning" functions within the framework of oxidative stress response. We further propose DR2231 protein as an evolutionary precursor of dimeric dUTPases.

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Dimeric dUTPases, HisE, and MazG belong to a New Superfamily of all-α NTP Pyrophosphohydrolases with Potential “House-cleaning” Functions

Cited by 79 publications

References 70 publications

Preventive DNA repair by sanitizing the cellular (deoxy)nucleoside triphosphate pool

Preventive DNA repair by sanitizing the cellular (deoxy)nucleoside triphosphate pool

Genomic and phenotypic characterization of Rhizobium gallicum phage vB_RglS_P106B

Structural and Functional Insights into DR2231 Protein, the MazG-like Nucleoside Triphosphate Pyrophosphohydrolase from Deinococcus radiodurans

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