ライフサイエンスコーパス: dUTPase

1 dUTPase genes were cloned and expressed from two other c

2 dUTPase is a ubiquitous and essential enzyme responsible

3 dUTPase is an enzyme essential for depleting potentially

4 dUTPase is encoded as an auxiliary gene in a number of v

5 dUTPase, which eliminates dUTP from the DNA biosynthetic

6 dUTPases catalyze the hydrolysis of dUTP into dUMP and p

7 dUTPases convert dUTP to dUMP, thus avoiding the misinco

8 mperature optimum (37 degrees C) than PBCV-1 dUTPase (50 degrees C).

9 o dUTPases have similar properties to PBCV-1 dUTPase except that IL-3A dUTPase has a lower temperatur

10 In type 1 dUTPases, Stl binding is inhibited by dUTP.

11 includes three distinct enzyme families: (1) dUTPases in trypanosomatides, C.jejuni and several other

12 we show that varphiNM1 dut encodes a type 2 dUTPase (DutNM1), which has an alpha-helical structure t

13 The IL-3A dUTPase differs from the PBCV-1 enzyme by nine amino aci

14 operties to PBCV-1 dUTPase except that IL-3A dUTPase has a lower temperature optimum (37 degrees C) t

15 P45 was shown to function as a dUTPase, converting dUTP to dUMP and inorganic pyrophosp

16 roducts, bacterial genes and, in one case, a dUTPase from a eukaryotic virus.

17 Many DNA viruses and retroviruses encode a dUTPase or uracil-DNA glycosylase (UNG) to counteract ur

18 zyme activity were then lost, resulting in a dUTPase containing a single active site with different e

19 The ORF54-encoded protein is a dUTPase; however, dUTPase activity is neither necessary

20 enzymatically active and immunoreacts with a dUTPase-specific monoclonal antibody.

21 es have evolved from an ancestral adenovirus dUTPase and, from this structural framework, developed n

22 o assess the involvement of dUTP binding and dUTPase activity in derepression by DutNM1.

23 Although dCTP deaminase and dUTPase activities are usually found in separate but hom

24 a combined deficiency of exonuclease III and dUTPase, which has been attributed to unrepaired abasic

25 r detectable enzymatic activity, E4 ORF1 and dUTPase proteins were predicted to possess strikingly si

26 nal similarity was found for the E4 ORF1 and dUTPase proteins, we propose that human adenovirus E4 OR

27 In vivo, archaeal dUTPases may play an essential role in preventing dUTP i

28 alpha fold and are unrelated to the all-beta dUTPases of the majority of organisms including eukaryot

29 tissues and examined the association between dUTPase expression and response to 5-fluorouracil (5-FU)

30 To examine the association between dUTPase expression and response to 5-FU-based chemothera

31 that the relative expression levels of both dUTPase and uracil-DNA glycosylase can have great influe

32 Both dUTPases can interact with the SaPIbov1 Stl master repre

33 molecular replacement using Escherichia coli dUTPase as search model.

34 Crystallized single-copy dUTPases have been shown to assemble as homotrimers.

35 Variable cytoplasmic dUTPase expression was observed in these tumors; however

36 tive bacteria and their phages, and (3) dCTP/dUTPases in enterobacterial T4-like phages.

37 e proteins: dihydrofolate reductase, dCTPase-dUTPase, deoxyribonucleoside monophosphokinase, ribonucl

38 e, aerobic ribonucleotide reductase, dCTPase-dUTPase, gene 32 single-strand DNA-binding protein, and

39 icant similarity to bacterial dCTP deaminase/dUTPase and DNA flavoprotein, respectively.

40 Structure-guided analysis of the new dimeric dUTPase family revealed its sequence relationship to the

41 mechanism of dUTP/dUDP hydrolysis by dimeric dUTPases.

42 representative of the new family of dimeric dUTPases to be structurally characterised.

43 TP pyrophosphatases, suggesting that dimeric dUTPases evolved from a tetrameric MazG-like ancestor by

44 Therefore, dimeric dUTPases can be considered as candidate drug targets.

45 umerous X-ray crystal structures of distinct dUTPase and nucleoside phosphate complexes, which report

46 That two structurally distinct dUTPases bind the same repressor led us to speculate tha

47 lpha and phiNM1 encode structurally distinct dUTPases, Dut80alpha (type 1) and DutNM1 (type 2).

48 l observation that oxaliplatin downregulates dUTPase expression may provide a mechanistic basis contr

49 onstrate a role for E2F-1 and Sp1 in driving dUTPase expression.

50 We show how duplicated dUTPases might fold into a monomer, and we hypothesize t

51 Nucleotide pool sanitizing enzymes Dut (dUTPase), RdgB (dITPase), and MutT (8-oxo-dGTPase) of Es

52 a recombinant expressing VP5 from an early (dUTPase) or another leaky-late (VP16) promoter exhibited

53 re deleted and replaced with a strong early (dUTPase), an equal-strength leaky-late (VP16), or a stri

54 ance and should be of general relevance.EIAV dUTPase is a homotrimer where each subunit folds into a

55 erived macrophages with the anti-EBV-encoded dUTPase Ab 7D6 or the anti-TLR2 Ab blocked the productio

56 we demonstrate that the purified EBV-encoded dUTPase activates NF-kappaB in a dose-dependent manner t

57 naling pathways activated by the EBV-encoded dUTPase and to determine its role in modulating immune r

58 was abrogated by anti-TLR2, anti-EBV-encoded dUTPase blocking Abs and the overexpression of a dominan

59 However, the role of EBV-encoded dUTPase in DC activation/function and its potential cont

60 onocyte-derived macrophages with EBV-encoded dUTPase induces the expression of proinflammatory cytoki

61 importantly, we demonstrate that EBV-encoded dUTPase is secreted in exosomes from chemically induced

62 these findings suggest that the EBV-encoded dUTPase may act as an intercellular signaling molecule c

63 eome array studies revealed that EBV-encoded dUTPase modulates DC immune responses by inducing the se

64 esent study, we demonstrate that EBV-encoded dUTPase significantly altered the expression of genes in

65 nd neutralizing antibody against EBV-encoded dUTPase were compared in the three patient groups.

66 er, the receptor responsible for EBV-encoded dUTPase-mediated biological effects is not known.

67 DCs) may also be a target of the EBV-encoded dUTPase.

68 ed the production of IL-6 by the EBV-encoded dUTPase.

69 at the trimeric staphylococcal phage encoded dUTPases (Duts) are signaling molecules that act analogo

70 The trimeric staphylococcal phage-encoded dUTPases (Duts) are signalling molecules that induce the

71 The 5' region of the gene encoding dUTPase was isolated and characterized by a combination

72 criptional link between the essential enzyme dUTPase and the tumor suppressor p53.

73 kidney tsA201 cells, transiently expressing dUTPase showed that this protein is present predominantl

74 in vitro demonstrates that the P. falciparum dUTPase constitutes a valid and attractive novel target

75 ools for further investigating P. falciparum dUTPase for the development of much-needed novel antimal

76 nd selective inhibitors of the P. falciparum dUTPase that show drug-like properties and represent goo

77 ounds were assayed against both P.falciparum dUTPase and intact parasites.

78 Pase vs. 249 +/- 70 pg/mL in SA negative for dUTPase antibody).

79 ng an AMI and who were antibody positive for dUTPase (ANOVA p=0.008; 369 +/- 183 pg/mL in AMI and pos

80 8; 369 +/- 183 pg/mL in AMI and positive for dUTPase vs. 249 +/- 70 pg/mL in SA negative for dUTPase

81 activity mutants were created and tested for dUTPase activity using a novel NMR-based assay.

82 lted in a coding region comprising two fused dUTPase domains.

83 the human adenovirus E4 ORF1s, was a genuine dUTPase enzyme.

84 The recombinant protein has dUTPase activity and requires Mg(2+) for optimal activit

85 onal genes were derived from the herpesvirus dUTPase gene, probably by duplication.

86 ing a protein that is related to herpesvirus dUTPases but has a different and as yet unrecognized fun

87 CD4+ T cells, because these cells have high dUTPase activity (low dUTP), and only modest levels of h

88 DCD-DUT is a hexamer, unlike the homologous dUTPases, and its subunits contain several insertions an

89 ORF54-encoded protein is a dUTPase; however, dUTPase activity is neither necessary nor sufficient for

90 predicted amino-terminal sequence for human dUTPase.

91 nuclear and mitochondrial isoforms of human dUTPase.

92 zyme, which exhibits 92% identity with human dUTPase; the N-terminal extra 62-amino acid residue regi

93 erfamilies: MutT-related (Nudix) hydrolases, dUTPase, ITPase (Maf/HAM1) and all-alpha NTP pyrophospha

94 resents the first clinical study implicating dUTPase overexpression as a mechanism of resistance to T

95 upport the idea that small loop movements in dUTPase allow the shuttlingof the nucleotides between th

96 his hidden pocket and product is released in dUTPases is unresolved because of conflicting crystallog

97 dut-1 defect in Escherichia coli inactivates dUTPase, causing increased uracil incorporation in DNA a

98 Homologues of the C.jejuni dUTPase have been identified in several other bacteria a

99 The X-ray structure of the C.jejuni dUTPase in complex with the non-hydrolysable substrate a

100 These data support HERV-K dUTPase as a potential contributor to psoriasis pathophy

101 ntibody responses against recombinant HERV-K dUTPase in psoriasis patients compared with controls (P<

102 en conducted to determine the role of HERV-K dUTPase in psoriasis.

103 a support an independent role for the HERV-K dUTPase on psoriasis susceptibility, and suggest the nee

104 her T-cell responses against a single HERV-K dUTPase peptide (P<0.05).

105 demonstrate that wild-type and mutant HERV-K dUTPase proteins induce the activation of NF-kappaB thro

106 imary cells with wild-type and mutant HERV-K dUTPase proteins triggered the secretion of T(H)1 and T(

107 fter adjusting the association of the HERV-K dUTPase variants for the potential confounding effects o

108 and case-control association study of HERV-K dUTPase variants in 708 psoriasis cases and 349 healthy

109 Five common HERV-K dUTPase variants were found to be highly associated with

110 For this purpose, we constructed an HERV-K dUTPase wild-type sequence, as well as specific mutation

111 d the human endogenous retrovirus K (HERV-K) dUTPase located within the PSORS1 locus in the major his

112 dUDP binding not observed in the other known dUTPase structures.

113 [32P]Orthophosphate-labeled dUTPase was purified from HeLa cells, revealing that onl

114 ant and wild-type forms of p53 in modulating dUTPase promoter activity.

115 The in silico data further revealed a new dUTPase conformation on the pathway to a relatively open

116 Nuclear dUTPase staining within these tumors was also associated

117 Of the patients lacking nuclear dUTPase expression, 6 responded to 5-FU-based chemothera

118 ates that low intratumoral levels of nuclear dUTPase protein expression is associated with response t

119 Conversely, high levels of nuclear dUTPase protein expression predict for tumor resistance

120 s with tumors demonstrating positive nuclear dUTPase expression (P = 0.09).

121 Of the patients presenting positive nuclear dUTPase expression, 0 responded to chemotherapy, 1 had s

122 In normal tissues, nuclear dUTPase staining was observed exclusively in replicating

123 erium tuberculosis dUTP nucleotidohydrolase (dUTPase) has been determined at 1.3 Angstrom resolution

124 dUTP nucleotidohydrolase (dUTPase) is the key regulator of dUTP pools, and signifi

125 oxyuridine triphosphate nucleotidohydrolase (dUTPase) catalyzes the hydrolysis of dUTP to dUMP and PP

126 oxyuridine triphosphate nucleotidohydrolase (dUTPase) encoded by a human endogenous retrovirus K (HER

127 uridine 5'-triphosphate nucleotidohydrolase (dUTPase) from parasitic protozoa.

128 oxyuridine triphosphate nucleotidohydrolase (dUTPase) modulates innate immunity in human primary mono

129 uridine 5'-triphosphate nucleotidohydrolase (dUTPase), an enzyme involved in nucleotide metabolism th

130 oxyuridine triphosphate nucleotidohydrolase (dUTPase), produced following reactivation of Epstein Bar

131 oxyuridine triphosphate nucleotidohydrolase (dUTPase; EC 3.6.1.23) was purified from HeLa cells by im

132 The activities of dUTPase and uracil-DNA glycosylase, key enzymes in uraci

133 A comprehensive analysis of dUTPase amino acid sequence relationships was performed

134 phosphorylated, a more in depth analysis of dUTPase phosphorylation was undertaken.

135 e site of attack and shows the capability of dUTPase to cleave the dUTP analogue alpha,beta-imido-dUT

136 In contrast, depletion of dUTPase activity leads to the accumulation of dUTP pools

137 In contrast, depletion of dUTPase in HT29 cells did not substantially affect chemo

138 Thus, immunohistochemical detection of dUTPase in colon cancers provides distinct intracellular

139 -dependent transcriptional downregulation of dUTPase not observed in the isogenic null cell line.

140 blished work has indicated that evolution of dUTPase in the class of herpesviruses that infect mammal

141 ndent In contrast, cytoplasmic expression of dUTPase does not correlate with proliferation status and

142 uorouracil (5-FU) and elevated expression of dUTPase is negatively correlated with clinical response

143 colon cancer tumor specimens, expression of dUTPase was shown to be highly variable in both amount a

144 cate that the lower molecular weight form of dUTPase (DUT-N) is associated with the nucleus, while th

145 Each form of dUTPase has a distinct cellular localization.

146 lls, revealing that only the nuclear form of dUTPase is phosphorylated.

147 these data suggest that the nuclear form of dUTPase may be a target for cyclin-dependent kinase phos

148 n subunit association of the nuclear form of dUTPase.

149 hese analyses indicate that the two forms of dUTPase are largely identical, differing only in a short

150 ite the structural difference, both forms of dUTPase exhibited identical binding characteristics for

151 e gel electrophoresis, two distinct forms of dUTPase were evident in the purified preparation.

152 The identification of dUTPase as a PPAR-interacting protein suggests a possibl

153 tion and indicate that partial inhibition of dUTPase is a viable therapeutic approach to enhance the

154 this work and determine if both isoforms of dUTPase are phosphorylated, a more in depth analysis of

155 stinct nuclear and mitochondrial isoforms of dUTPase in human cells, reporting the cDNA sequence of t

156 port, we identified two distinct isoforms of dUTPase in human cells.

157 termined the effects of decreasing levels of dUTPase on sensitivity to the thymidylate synthase (TS)

158 proteins lacked conserved protein motifs of dUTPase enzymes or detectable enzymatic activity, E4 ORF

159 e have determined the expression patterns of dUTPase in normal and neoplastic tissues and examined th

160 Patterns of dUTPase protein expression observed included exclusive n

161 placement with Ala blocks phosphorylation of dUTPase in vivo.

162 To validate the potential of dUTPase as a target for drug development, we used small

163 The X-ray structures of dUTPase from equine infectious anaemia virus (EIAV) in u

164 The suppression of dUTPase by oxaliplatin promoted increased levels of dUTP

165 Suppression of dUTPase in SW620 and MCF-7 cells resulted in a significa

166 onal differences between arginine fingers of dUTPases and NTPases are explained on the basis of the u

167 Cells overexpressing dUTPase were protected from cytotoxicity by their abilit

168 Pfu dUTPase improves the yield of products amplified with Pf

169 ination of cloned Pfu DNA polymerase and Pfu dUTPase (PfuTurbo DNA polymerase) can amplify longer tar

170 other Gram-negative bacteria, (2) predicted dUTPases in various Gram-positive bacteria and their pha

171 pro-inflammatory action of the early protein dUTPase that is produced even during incomplete viral re

172 cellular enveloped virus host range protein, dUTPase, hydroxysteroid dehydrogenase, superoxide dismut

173 L8, pUL20, pUL32, pUL40 (RR2), pUL42, pUL50 (dUTPase), and Rsp40/ICP22.

174 e chemistry performed by the pyrophosphatase dUTPases.

175 f organismal and viral dUTP pyrophosphatase (dUTPase) enzymes.

176 oviruses either encode dUTP pyrophosphatase (dUTPase) or package host-derived uracil DNA glycosylase

177 inant Escherichia coli dUTP pyrophosphatase (dUTPase), an essential enzyme preventing incorporation o

178 Full-length rat dUTPase prevents PPAR-retinoid X receptor heterodimeriza

179 the N-terminal 62-amino acid segment of rat dUTPase.

180 In vitro binding assays indicate that rat dUTPase interacts with all three isoforms of mouse PPAR,

181 Northern blot hybridization shows that rat dUTPase is encoded by an abundant 1kilobase mRNA species

182 re, using the Mason-Pfizer monkey retrovirus dUTPase, we study the dUTPase-catalyzed hydrolysis of dU

183 pping arginine-rich motifs, and a C-terminal dUTPase-like structure.

184 utNM1 is active in Stl derepression and that dUTPase activity is not necessary for the mobilization o

185 ious work, this laboratory demonstrated that dUTPase is posttranslationally phosphorylated on serine

186 the same repressor led us to speculate that dUTPase activity may be important to the derepression pr

187 Recent evidence suggests that dUTPases may also represent a selective drug target in m

188 n treatment induced enrichment of p53 at the dUTPase promoter with a concomitant reduction in Sp1.

189 e such SaPI, SaPIbov1, is derepressed by the dUTPase (Dut) of bacteriophage 80alpha (Dut80alpha) and

190 ound that recombinant viruses containing the dUTPase promoter inserted in the VP5 locus expressed VP5

191 uencing a 4,245-bp region which contains the dUTPase gene, part of a putative spliced DNA polymerase

192 ertions and substitutions different from the dUTPase beta barrel core that likely contribute to dCTP

193 (chr15.hg19:g.48,626,619A>G) located in the dUTPase (DUT) gene (National Center for Biotechnology In

194 o and in vitro, leading to inhibition of the dUTPase activity and Stl release from its target DNA.

195 The crystal structure of the dUTPase from the important gastric pathogen Campylobacte

196 the first functional characterization of the dUTPase promoter and demonstrate a role for E2F-1 and Sp

197 Combining mass spectrometry analysis of the dUTPase-catalyzed reaction carried out in and quantum me

198 e-rRNA levels, and this was dependent on the dUTPase-like motif in pUL31.

199 uctural and biochemical methods to study the dUTPase from Mycobacterium tuberculosis In particular, t

200 izer monkey retrovirus dUTPase, we study the dUTPase-catalyzed hydrolysis of dUTP, an incorrect DNA b

201 EBV infection, our results suggest that the dUTPase could be a potential target for the development

202 These analyses demonstrate that the dUTPase isoforms are encoded by the same gene with isofo

203 C-terminal region different from that of the dUTPases and possible mechanisms for both bifunctional e

204 A comparison of the dUTPases from C.jejuni and Trypanosoma cruzi reveals a c

205 ditional studies to clarify the role of this dUTPase in the pathogenesis of psoriasis.

206 f the active centre established for trimeric dUTPase structures, in which subunit interfaces form thr

207 of a conserved arginine residue in trimeric dUTPases that meets all the criteria established for arg

208 A putative deoxyuridine triphosphatase (dUTPase) gene from chlorella virus PBCV-1 was cloned, an

209 identified rat deoxyuridine-triphosphatase (dUTPase, EC 3.6.1.23) as a PPARalpha-interacting protein

210 monomer, and we hypothesize that triplicated dUTPases also assemble as monomers.

211 g a specific inhibitor of the M.tuberculosis dUTPase enzyme.

212 been proposed that inhibiting M.tuberculosis dUTPase might be an effective means to treat tuberculosi

213 The two dUTPases have similar properties to PBCV-1 dUTPase excep

214 enetic analysis revealed at least five viral dUTPase sequence lineages in well-supported monophyletic

215 ows that tegument protein VP22 and the viral dUTPase, encoded by genes UL49 and UL50, respectively, a

216 PPARalpha when PPARalpha is coexpressed with dUTPase.

217 content was increased, Pfu formulations with dUTPase exhibited significantly higher efficiencies than

218 Interaction of PPARalpha with dUTPase is with the N-terminal 62-amino acid segment of

219 repair transactions cannot be redundant with dUTPase and instead reveal "defect-damage-repair" cycles