ライフサイエンスコーパス: dTDP

1 we show that the loss of Drosophila TDP-43 (dTDP-43) results in an increased production of sensory b

2 the appropriate dimensions to accommodate a dTDP-linked sugar.

3 It is synthesized in these organisms as a dTDP-linked sugar via the action of five enzymes.

4 It is produced in these organisms as a dTDP-linked sugar, with five enzymes ultimately required

5 Escherichia coli gene wbbL, which encodes a dTDP-Rha:alpha-D-GlcNAc-pyrophosphate polyprenol, alpha-

6 One of the genes, desIV, codes for a dTDP-glucose 4,6-dehydratase, which is referred to as De

7 ing that the enzyme encoded by the gene is a dTDP-beta-L-rhamnose alpha-1,3-L-rhamnosyl transferase t

8 reading frame (ORF) with homology to rmlC, a dTDP-rhamnose biosynthetic gene.

9 other PPases such as Pseudomonas aeruginosa dTDP-Glc PPase and Salmonella typhi CDP-Glc PPase.

10 AknK also accepts an alternate dTDP-L-sugar, dTDP-L-daunosamine, and other monoglycosyl

11 ere evaluated using a the substrate analogue dTDP-xylose.

12 The substrate analogue, dTDP-xylose, was used to investigate the effects of the

13 r action as dTDP-glucose-4,6-dehydratase and dTDP-4-keto-6-deoxyglucose-3,5-epimerase enzymes respect

14 -deoxysugar donors, dTDP-L-2-deoxyfucose and dTDP-L-daunosamine, and the monoglycosyl aglycone, rhodo

15 phosphorylation of dGMP and dTMP to dGDP and dTDP, respectively, by using either GTP, dGTP or dTTP as

16 The structure of WsaF bound to dTDP and dTDP-beta-l-rhamnose coupled to biochemical analysis ide

17 rmation of UDP-Glc, UDP-Gal, UDP-GalNAc, and dTDP-Rha.

18 irement for GDP-d-mannose, UDP-d-glucose and dTDP-l-rhamnose in Psl production and surface attachment

19 izes glucosyl C4 of dTDP-glucose to NADH and dTDP-4-ketoglucose.

20 hamnose biosynthesis through their action as dTDP-glucose-4,6-dehydratase and dTDP-4-keto-6-deoxygluc

21 hamnose biosynthesis pathway is catalyzed by dTDP-4-dehydrorhamnose reductases (RmlD).

22 etic mechanism for the reaction catalyzed by dTDP-glucose 4,6-dehydratase (4,6-dehydratase) has been

23 ed by the pH dependence of NADH formation by dTDP-xylose, is 6.41.

24 RmlA is inhibited by dTDP-L-rhamnose thereby regulating L-rhamnose production

25 DP-4-keto-6-deoxyglucose by Escherichia coli dTDP-glucose 4,6-dehydratase (4,6-dehydratase) takes pla

26 Escherichia coli dTDP-glucose 4,6-dehydratase and UDP-galactose 4-epimera

27 A model of the Escherichia coli dTDP-glucose-4,6-dehydratase (4,6-dehydratase) active si

28 and a 4-keto reductase that together convert dTDP-4-keto-6-deoxy-Glc to dTDP-beta-l-rhamnose.

29 tep in d-kijanose biosynthesis by converting dTDP-3-amino-2,3,6-trideoxy-4-keto-3-methyl-d-glucose in

30 and purified from, Escherichia coli converts dTDP-4-keto-6-deoxy-Glc to dTDP-beta-l-rhamnose in the p

31 ction mixtures containing recombinant Cps2T, dTDP-rhamnose, and the Cps2E product (undecaprenyl pyrop

32 ive substrate, dTDP-6-fluoro-6-deoxyglucose (dTDP-6FGlc), which undergoes fluoride ion elimination in

33 sphate)(dTMP-PCP), thymidine 5'-diphosphate (dTDP), adenosine 5'-triphosphate (ATP), and adenosine 5'

34 ar donor, 2'-deoxy-thymidine 5'-diphosphate (dTDP)-beta-L-4-epi-vancosamine.

35 e preparation of dTDP-L-2-deoxysugar donors, dTDP-L-2-deoxyfucose and dTDP-L-daunosamine, and the mon

36 complexes of the enzyme with CoA and either dTDP-D-Quip3N or dTDP-3-amino-3,6-didexoy-alpha-D-galact

37 ArnA resembles UDP-galactose epimerase, dTDP-glucose-4,6-dehydratase, and UDP-xylose synthase in

38 r nucleotides, like UDP-galactose epimerase, dTDP-glucose-4,6-dehydratase, and UDP-xylose synthase.

39 rmed that GAS RmlB and RmlC are critical for dTDP-L-rhamnose biosynthesis through their action as dTD

40 transcribed with three of the four genes for dTDP-Rha biosynthesis (i.e., rmlA, rmlC, and rmlB).

41 ) for NADPH is 90 microm and 16.9 microm for dTDP-4-keto-6-deoxy-Glc.

42 ween C5 and C6 of dTDP-4-ketoglucose to form dTDP-4-ketoglucose-5,6-ene.

43 s of dTDP-6-deoxy-D-xylo-4-hexulose, forming dTDP-6-deoxy-L-lyxo-4-hexulose.

44 osyl-(1->4)-D-glucopyranose is produced from dTDP-4-amino-4,6-dideoxy-D-glucose and maltose by the gl

45 dTDP-3-amino-3,6-didexoy-alpha-D-galactose (dTDP-D-Fucp3N).

46 m inhibitory lead compounds that bind to GAS dTDP-rhamnose biosynthesis enzymes RmlB, RmlC and GacA.

47 Hence, dTDP-rhamnose biosynthesis is essential for the growth o

48 In dTDP-43 mutants, miR-9a expression is significantly redu

49 mportantly, we confirmed that Ri03 inhibited dTDP-L-rhamnose formation in a concentration-dependent m

50 The conversion of dTDP-glucose into dTDP-4-keto-6-deoxyglucose by Escherichia coli dTDP-gluc

51 complexed to S-adenosylhomocysteine and its dTDP-linked sugar product.

52 dTTP; 6 x 10(-7) M, dTMP-PCP; 4 x 10(-6) M, dTDP; 3 x 10(-5) M, ATP; 2 x 10(-6) M, ATP gamma S), whi

53 Remarkably, the thyA mutant that makes dTDP-glucose and initiates ECA synthesis normally yet ca

54 ly GT-2, in complex with both Mn-dTDP and Mg-dTDP at a resolution of 2 A.

55 ve from family GT-2, in complex with both Mn-dTDP and Mg-dTDP at a resolution of 2 A.

56 w-molecular-weight (LMW)-dT source as mostly dTDP-glucose and its derivatives, used to synthesize ent

57 Neither dTDP nor dGDP is a phosphate acceptor of nucleoside trip

58 The sugar nucleotide dTDP-L-rhamnose is critical for the biosynthesis of the

59 luster of genes encoding the biosynthesis of dTDP-deoxyallose.

60 enzymes are required for the biosynthesis of dTDP-desosamine in Streptomyces venezuelae, with the las

61 the enzymes involved in the biosynthesis of dTDP-Fucp3NAc is a 3,4-ketoisomerase, hereafter referred

62 d a four-gene operon for the biosynthesis of dTDP-L-rhamnose, an essential precursor for the sphingan

63 lar to genes involved in the biosynthesis of dTDP-rhamnose, glycosyltransferases, and ABC transporter

64 ich NAD(+) initially oxidizes glucosyl C4 of dTDP-glucose to NADH and dTDP-4-ketoglucose.

65 xt, water is eliminated between C5 and C6 of dTDP-4-ketoglucose to form dTDP-4-ketoglucose-5,6-ene.

66 Hydride transfer from NADH to C6 of dTDP-4-ketoglucose-5,6-ene regenerates NAD(+) and produc

67 nospora chalcea, catalyzes the conversion of dTDP-3-amino-2,3,6-trideoxy-4-keto-D-glucose to dTDP-3-a

68 The steady-state rate of conversion of dTDP-6FGlc to dTDP-4-keto-6-deoxyglucose by each Asp135

69 The conversion of dTDP-glucose into dTDP-4-keto-6-deoxyglucose by Escheric

70 cose 4,6-dehydratase catalyzed conversion of dTDP-glucose to dTDP-4-keto-6-deoxyglucose occurs in thr

71 e, transient appearance and disappearance of dTDP-hexopyranose-5,6-ene (the reductively stabilized dT

72 he phosphotransfer reaction for formation of dTDP from dTMP is a new strategy for anticancer treatmen

73 In bacteria, formation of dTDP-rhamnose requires three enzymes.

74 We therefore conclude that inhibitors of dTDP-L-rhamnose biosynthesis, such as Ri03, affect strep

75 help future screens for novel inhibitors of dTDP-L-rhamnose biosynthesis.

76 Overexpression of dTDP-43 causes both loss and ectopic production of SOPs.

77 We conclude that: 1) the significant pool of dTDP-hexoses delays acute T-starvation; 2) T-starvation

78 pimerization of the C3' and C5' positions of dTDP-6-deoxy-D-xylo-4-hexulose, forming dTDP-6-deoxy-L-l

79 enzymes, AknK, as well as the preparation of dTDP-L-2-deoxysugar donors, dTDP-L-2-deoxyfucose and dTD

80 , the 4A' hexamers formed in the presence of dTDP with or without Mg2+ did not bind DNA, indicating t

81 stals of KijD3 were grown in the presence of dTDP, and the structure was solved to 2.05-A resolution.

82 -type helicase, binds DNA in the presence of dTDP.

83 rs is nearly the converse in the presence of dTDP.

84 x enzymes are required for the production of dTDP-desosamine.

85 f the enzymes required for the production of dTDP-Fucp3NAc.

86 es the penultimate step in the production of dTDP-Quip3NAc.

87 The transient formation and reaction of dTDP-4-ketoglucose could not be observed, because this i

88 nts for most of the steps of the reaction of dTDP-glucose-d(7) to be evaluated.

89 phatase (dTTPase) reaction is the release of dTDP.

90 4, Tyr160, and Lys164, in the active site of dTDP-glucose 4,6-dehydratase.

91 growth of mycobacteria and the targeting of dTDP-rhamnose synthesis for new tuberculosis drugs is su

92 for a new family of enzymes that function on dTDP-linked sugar substrates.

93 enzyme with CoA and either dTDP-D-Quip3N or dTDP-3-amino-3,6-didexoy-alpha-D-galactose (dTDP-D-Fucp3

94 vation, we show that QdtB can also turn over dTDP-3-acetamido-3,6-dideoxy-alpha-d-galactose.

95 e synthesis of deoxy-thymidine di-phosphate (dTDP)-L-rhamnose, an important component of the cell wal

96 osynthesis of the nucleotide sugar precursor dTDP-L-rhamnose is critical for the viability and virule

97 regenerates NAD(+) and produces the product dTDP-4-keto-6-deoxyglucose.

98 DesI was solved in complex with its product, dTDP-4-amino-4,6-dideoxyglucose, to a nominal resolution

99 crystallized in the presence of its product, dTDP-Quip3N, and the structure was solved and refined to

100 drogen-solvent exchange reaction of product, dTDP-4-keto-6-deoxyglucose.

101 glycosyl transferase, and orfde6, a putative dTDP-rhamnose biosynthesis gene, generated two OG1RF mut

102 Streptococcal pathogens require dTDP-L-rhamnose for the production of structurally simil

103 the fraction of NADH formed with saturating dTDP-xylose show shifts in the pK(a) assigned to Tyr160

104 pyranose-5,6-ene (the reductively stabilized dTDP-4-ketoglucose-5,6-ene), and the appearance of produ

105 The final step of the four-step dTDP-L-rhamnose biosynthesis pathway is catalyzed by dTD

106 he glycosyltransferases, the donor substrate dTDP-rhamnose was first synthesized using recombinant S.

107 zed as a complex with NAD+ and the substrate dTDP-glucose and its structure determined to 1.35 A reso

108 -terminal domain, which binds the substrate (dTDP-beta-l-rhamnose).

109 as performed using an alternative substrate, dTDP-6-fluoro-6-deoxyglucose (dTDP-6FGlc), which undergo

110 P-benzene binding mode, the DesVI substrate, dTDP-3-(methylamino)-3,4,6-trideoxyglucose, has been mod

111 AknK also accepts an alternate dTDP-L-sugar, dTDP-L-daunosamine, and other monoglycosylated anthracyc

112 -vancosamine from the chemically synthesized dTDP-4-epi-vancosamine to the beta-OH-Tyr6 residue of th

113 t of a new class of antibiotics that targets dTDP-rhamnose biosynthesis in pathogenic bacteria.

114 tion studies further support the notion that dTDP-43 acts through miR-9a to control the precision of

115 The dTDP moiety is anchored to the protein via the side chai

116 The dTDP-glucose 4,6-dehydratase catalyzed conversion of dTD

117 The dTDP-L-rhamnose complex identifies how the protein is co

118 ino acid side chains involved in binding the dTDP-sugar into the active site include Tyr 183, His 309

119 The first enzyme in the dTDP-L-rhamnose biosynthetic pathway is glucose-1-phosph

120 either of two mechanisms, enolization of the dTDP-4-ketoglucose intermediate, followed by elimination

121 es in the first hydride transfer step of the dTDP-glucose 4,6-dehydratase mechanism has been studied

122 spectively from the 4'-hydroxyl group of the dTDP-glucose substrate.

123 s between the pyranosyl C-4' hydroxyl of the dTDP-sugar and the protein.

124 ble for anchoring the hexose moieties of the dTDP-sugars to the protein include Glu 141, Asn 159, and

125 which in turn is three times faster than the dTDP release rate.

126 It was determined that the dTDP-rhamnose synthesis gene, rmlD, could be inactivated

127 llelic exchange in rmlD, another ORF in this dTDP-rhamnose biosynthetic cluster.

128 dy-state rate of conversion of dTDP-6FGlc to dTDP-4-keto-6-deoxyglucose by each Asp135 variant was id

129 The structure of WsaF bound to dTDP and dTDP-beta-l-rhamnose coupled to biochemical ana

130 nation to dTDP-4-ketoglucose, dehydration to dTDP-4-ketoglucose-5,6-ene, and rereduction of C6 to the

131 tive site in three steps: dehydrogenation to dTDP-4-ketoglucose, dehydration to dTDP-4-ketoglucose-5,

132 The enzyme phosphorylates dTMP and dGMP to dTDP and dGDP, respectively, in the presence of a phosph

133 hia coli converts dTDP-4-keto-6-deoxy-Glc to dTDP-beta-l-rhamnose in the presence of NADPH.

134 together convert dTDP-4-keto-6-deoxy-Glc to dTDP-beta-l-rhamnose.

135 P-3-amino-2,3,6-trideoxy-4-keto-D-glucose to dTDP-3-amino-2,3,6-trideoxy-4-keto-3-methyl-D-glucose.

136 tase catalyzed conversion of dTDP-glucose to dTDP-4-keto-6-deoxyglucose occurs in three sequential ch

137 the subunit-subunit interfaces, and the two dTDP-sugar ligands employed in this study bind to the pr

138 To expand the repertoire of UDP/dTDP sugars readily available for glycorandomization, we

139 tion of the second sugar to the chain, using dTDP-L-2-deoxyfucose and rhodosaminyl aklavinone, to cre

140 to that of wt, in contrast to turnover using dTDP-glucose where differences in rates of up to 2 order

141 ction of a glycosyltransferase that utilizes dTDP-desosamine as its substrate.

142 This is in contrast to bacteria where dTDP-rhamnose is the activated form of this sugar.

143 ip between dGDP and both dGTP, dGMP, whereas dTDP appears to have a mixed type of inhibition of dTMP

144 The thyA mutant, in which dTDP-glucose production is blocked by the rfbA rffH muta

145 cture of this sugar isomerase complexed with dTDP and solved to 1.5 A resolution.

146 to 1.44 A of wild-type DesIV complexed with dTDP.