ライフサイエンスコーパス: dolichol

1 tic mechanism of the synthesis of GlcNAc-P-P-dolichol.

2 cNAc-P-P-dolichol but not that of GlcNAc-P-P-dolichol.

3 D1 overexpression or by supplementation with dolichol.

4 e-derived metabolites, such as ubiquinone or dolichol.

5 nthetic pathway that produces the LLO anchor dolichol.

6 or for cleavage of Glc(3)Man(9)GlcNAc(2)-P-P-dolichol.

7 Retinol, atRA glucuronide, 13-cis-RA, dolichol, 5,6-epoxy-RA, and vitamin D(3) did not compete

8 Man 7GlcNAc 2-PP-dolichol, a higher-order lipid intermediate, was flipped

9 lippase that translocates Man(5)GlcNAc(2)-PP-dolichol, a lipid intermediate of N-glycosylation.

10 and SlCPTBP localize to the ER, the site of dolichol accumulation and synthesis in eukaryotes.

11 GlcNAc-P-P-dolichol also exerts a stimulatory effect on the biosynt

12 The apparent K(i) values for GlcNAc-P-P-dolichol and GlcNAc-GlcNAc-P-P-dolichol under basal cond

13 hol; the apparent K(i) values for GlcNAc-P-P-dolichol and GlcNAc-GlcNAc-P-P-dolichol were 2.2 and 11

14 5 and Lec35 cells accumulate Man5GlcNAc2-P-P-dolichol and glucosaminyl-acylphosphatidylinositol.

15 In an alg11 lesion, both Man(3)GlcNAc(2)-PP-dolichol and Man(4)GlcNAc(2)-PP-dolichol are translocate

16 nthesis of glucose(3)mannose(9)GlcNAc(2)-P-P-dolichol and N-linked glycosylation.

17 ulated both eukaryotic (Glc3-Man9-GlcNAc2-PP-Dolichol) and bacterial (Glc1-GalNAc5-Bac1-PP-Undecapren

18 nylpyrophosphoryldolichol (GlcNAc-GlcNAc-P-P-dolichol), and product inhibition by GlcNAc-P-P-dolichol

19 GlcNAc(2)-PP-dolichol and Man(4)GlcNAc(2)-PP-dolichol are translocated into the ER lumen as substrate

20 ed oligosaccharide (LLO) Glc3Man9GlcNAc2-P-P-dolichol as measured with radioactive sugar precursors.

21 tein has a region homologous to the putative dolichol-binding region in the yeast ALG1 protein, but i

22 s expression in the Saccharomyces cerevisiae dolichol biosynthesis mutant (rer2) complemented the tem

23 rther show that the involvement of SlCPT3 in dolichol biosynthesis requires the participation of a di

24 inery yields insights into the regulation of dolichol biosynthesis.

25 tous expressions in lettuce, showed a potent dolichol biosynthetic activity in vitro.

26 k the de novo formation of GlcNAc-GlcNAc-P-P-dolichol but not that of GlcNAc-P-P-dolichol.

27 ol-P that was trapped as Glc3Man9GlcNAc2-P-P-dolichol by translation arrest.

28 complex, leading to free glycan release from dolichol carriers, as well as immune activation and auto

29 ates showed that MPD flippase recognizes the dolichol chain of MPD, preferring a saturated alpha-isop

30 ed in the synthesis of sterols, carotenoids, dolichols, coenzyme Q, heme a and farnesylated proteins.

31 e in plant cells which makes manipulation of dolichol content in plant tissues feasible.

32 mily (SlCPT3) resulted in a ~60% decrease in dolichol content.

33 p of the synthesis of the Man(5)GlcNAc(2)-PP-dolichol core oligosaccharide on the cytosolic face of t

34 es the factors mediating the key step of the dolichol cycle in plant cells which makes manipulation o

35 nce of an unexpected alternative pathway for dolichol de novo biosynthesis.

36 equired to complement the growth defects and dolichol deficiency of the yeast dolichol mutant, rer2.

37 ects although disturbances in other cellular dolichol-dependent processes could also contribute.

38 le for all known classes of monosaccharide-P-dolichol-dependent reactions in mammals.

39 nto the ER lumen as substrates for the Man-P-dolichol-dependent sugar transferases in this compartmen

40 er of a precursor Glc(3)Man(9)GlcNAc(2) from dolichol (Dol) to consensus Asn residues in nascent prot

41 ing of mass spectra of metabolically labeled dolichols (Dols), designed to quantitatively follow the

42 Supplementation of the human diet with dolichol-enriched plant tissues could allow new therapeu

43 esolved from the oligosaccharide-diphosphate dolichol flippase that translocates Man(5)GlcNAc(2)-PP-d

44 ucose(3)mannose(9)N-acetylglucosamine(2)-P-P-dolichol (G(3)M(9)Gn(2)-P-P-Dol) to asparaginyl residues

45 tion of tryptophanyl residues, and glucose-P-dolichol (GPD)-dependent glucosylation of LLO.

46 smic leaflet or is first dephosphorylated to dolichol has not been determined.

47 on by catalyzing the synthesis of GlcNAc-P-P-dolichol, has multiple transmembrane spans and a catalyt

48 me Q (a component of the respiratory chain), dolichols (important for protein glycosylation), and iso

49 responsible for conversion of polyprenol to dolichol in Arabidopsis thaliana.

50 The presence of residual dolichol in cells depleted for this enzyme suggests the

51 Shortage of dolichol in PPRD2-deficient cells is partially rescued b

52 talyzes the CTP-dependent phosphorylation of dolichol in the biosynthesis de novo and possibly the re

53 lcNAc2-P-P-dolichol to Glc0-3Man9GlcNAc2-P-P-dolichol in vivo.

54 Dolichol is a required cofactor for protein glycosylatio

55 Synthesis of Glc 3Man 9GlcNAc 2-PP-dolichol is initiated on the cytoplasmic side of the ER

56 The glycolipid Glc 3Man 9GlcNAc 2-PP-dolichol is the oligosaccharide donor for protein N-glyc

57 ucosaminylpyrophosphoryldolichol (GlcNAc-P-P-dolichol), is under investigation as a possible site of

58 in N-glycosylation, Glc(3)Man(9)GlcNAc(2)-PP-dolichol, is synthesized via a multistep pathway that st

59 ichol), and product inhibition by GlcNAc-P-P-dolichol itself.

60 Dolichol kinase (DK) catalyzes the CTP-dependent phospho

61 No changes in dolichol kinase activity were observed.

62 domain that is present in the SEC59-encoded dolichol kinase and CDS1-encoded CDP-diacylglycerol synt

63 zed for lipid intermediate biosynthesis, and dolichol kinase is not required for recycling.

64 5 and slr1652 indicated modest similarity to dolichol kinase.

65 icity of the glycosyl donor, three unnatural dolichol-linked disaccharide analogues (Dol-PP-GlcNTFA-G

66 Thus, control of the dolichol-linked Glc(3)Man(9)GlcNAc(2) supply gives the U

67 Inhibition of dolichol-linked Glc(3)Man(9)GlcNAc(2) synthesis by gluco

68 This study reports that conversion of dolichol-linked Man(2-5)GlcNAc(2) intermediates into mat

69 The dolichol-linked monosaccharide Dol-PP-GlcNAc 3 was found

70 to form dolichols, required for synthesis of dolichol-linked monosaccharides, and the oligosaccharide

71 t enzyme, near-homogeneous preparations of a dolichol-linked oligosaccharide (Glc(3)Man(9)GlcNAc(2)-P

72 isms by the addition of a second, regulatory dolichol-linked oligosaccharide binding site, the presen

73 ferase (OT), which catalyzes the transfer of dolichol-linked oligosaccharide chains to nascent polype

74 ssembled high-mannose oligosaccharide from a dolichol-linked oligosaccharide donor onto asparagine ac

75 preferentially utilizes the fully assembled dolichol-linked oligosaccharide Glc(3)Man(9)GlcNAc(2)-PP

76 The dolichol-linked oligosaccharide Glc3Man9GlcNAc2-PP-Dol i

77 oligosaccharides as well as a heterogeneous dolichol-linked oligosaccharide library.

78 lum with the synthesis of a highly conserved dolichol-linked oligosaccharide precursor.

79 The second step of dolichol-linked oligosaccharide synthesis in the N-linke

80 he synthesis of GDP-mannose, a substrate for dolichol-linked oligosaccharide synthesis.

81 Mature dolichol-linked oligosaccharides (mDLOs) needed for euka

82 ed donor substrate from a complex mixture of dolichol-linked oligosaccharides (OS-PP-Dol) has not bee

83 production, leading to diminished levels of dolichol-linked oligosaccharides and a broad reduction i

84 es cerevisiae using structurally homogeneous dolichol-linked oligosaccharides as well as a heterogene

85 However, many protist organisms assemble dolichol-linked oligosaccharides that lack glucose resid

86 The patients produced a truncated dolichol-linked precursor oligosaccharide with 5 mannose

87 hol, which is essential for the formation of dolichol-linked precursor oligosaccharides.

88 catalyzes the co-translational transfer of a dolichol-linked tetradecasaccharide (Dol-PP-GlcNAc(2)Man

89 nnose used to make Glc(3)Man(9)GlcNAc(2)-P-P-dolichol (lipid-linked oligosaccharide; LLO).

90 sformed cells that are known to have altered dolichol lipids.

91 of the lipid intermediate Man(5)GlcNAc(2)-PP-dolichol (M5-DLO) across the ER membrane.

92 lipping of the intermediate Man 5GlcNAc 2-PP-dolichol (M5-DLO) across the ER.

93 osynthetic lipid intermediate Man5GlcNAc2-PP-dolichol (M5-DLO) flips from the cytoplasmic to the lumi

94 transbilayer movement of Man(5)GlcNAc(2)-P-P-dolichol (M5-DLO), a series of experiments was conducted

95 f the glycolipid Man(5)GlcNAc(2)-diphosphate dolichol (Man(5)GlcNAc(2)-PP-Dol) across the endoplasmic

96 o observed under conditions where mannosyl-P-dolichol (Man-P-dol) stimulated the biosynthesis of GlcN

97 ich is preassembled onto a membrane-anchored dolichol molecule embedded within the endoplasmic reticu

98 Dolichol monophosphate (Dol-P) functions as an obligate

99 r utilization of the mannose donor mannose-P-dolichol (MPD) in synthesis of both lipid-linked oligosa

100 Mannose-phosphate-dolichol (MPD) is a multifunctional glycolipid that is s

101 and utilization, respectively, of mannose-P-dolichol (MPD).

102 defects and dolichol deficiency of the yeast dolichol mutant, rer2.

103 to translocate the glycolipid Man5GlcNAc2-PP-dolichol (needed to synthesize N-glycan precursors) acro

104 ent at the ER is also required for efficient dolichol oligosaccharide biosynthesis.

105 ges in concentrations of Glc3Man9GlcNAc2-P-P-dolichol or early LLO intermediates.

106 te of synthesis of [(3)H]Man(9)GlcNAc(2)-P-P-dolichol or Man(9)[(3)H]GlcNAc(2)-P-P-dolichol, respecti

107 nitiation by accumulated Glc3Man9GlcNAc2-P-P-dolichol, or inhibition of a GDP-mannose dependent trans

108 UDP-GlcNAc:dolichol-P GlcNAc-1-P transferase (GPT) is an endoplasmi

109 Hamster UDP-GlcNAc:dolichol-P GlcNAc-1-P transferase (GPT), which initiates

110 three transferases shared a limited pool of dolichol-P that was trapped as Glc3Man9GlcNAc2-P-P-dolic

111 ppears to make available a secondary pool of dolichol-P, masking inhibition by translation arrest, as

112 The GPT mutants had no effect on two other dolichol-P-dependent endoplasmic reticulum enzymes.

113 ll wall beta-1,6-glucan is indirect and that dolichol-P-glucose is not an intermediate in this pathwa

114 nthetic pathway, disappear in the absence of dolichol-P-glucose synthase (alg5Delta).

115 structed a double mutant, alg5Delta (lacking dolichol-P-glucose synthase) cwh41Delta, and found that

116 Except for dolichol-P-mannose, other precursors, including mannose,

117 results directly support the hypothesis that dolichol-P-P-oligosaccharide assembly is initiated in th

118 f GlcNAc-P-P-dolichol, the committed step of dolichol-P-P-oligosaccharide synthesis.

119 hesis depends upon a limited primary pool of dolichol-P.

120 s have enabled identification of most of the dolichol pathway enzymes in Saccharomyces cerevisiae, th

121 he Alg9 and Alg12 proteins, which act in the dolichol pathway for N-glycosylation.

122 Inhibition of the dolichol pathway of protein N-glycosylation also causes

123 which is the only glycosyltransferase in the dolichol pathway that has been expressed as an active pr

124 synthesis, requiring multiple cycles of the dolichol pathway, occurred in the absence of CTP.

125 erved between these two intermediates of the dolichol pathway.

126 inked glycoproteins proceeds by means of the dolichol pathway.

127 le of glycosyltransferases that comprise the dolichol pathway.

128 bound glycosyltransferases that comprise the dolichol pathway.

129 annose in this study, is added to a distinct dolichol phosphate carrier.

130 -83 are modified by a pentasaccharide, while dolichol phosphate is modified by a tetrasaccharide comp

131 Dolichol phosphate mannose (Dol-P-Man), formed upon tran

132 prenyl-glycosyltransferases (PI-GTs) include dolichol phosphate mannose synthase (DPMS), which genera

133 me time, cells grown at low salinity contain dolichol phosphate modified by a distinct tetrasaccharid

134 The gene encoding UDP-GlcNAc:dolichol phosphate N-acetylglucosamine-1-phosphate trans

135 first step of this pathway, the reaction of dolichol phosphate with UDP-GlcNAc to form N-acetylgluco

136 Dolichol phosphate, synthesized from the mevalonate path

137 .75 M NaCl) salt, as was the glycan bound to dolichol phosphate, the lipid upon which the N-linked gl

138 tical protein and regions with similarity to dolichol phosphate-D-mannose:protein O-D-mannosyltransfe

139 Archaea and eukaryotes share a dolichol phosphate-dependent system for protein N-glycos

140 GlcNAc and non-competitive inhibition toward dolichol phosphate.

141 ive toward UDP-GlcNAc and competitive toward dolichol phosphate.

142 Dolichol-phosphate mannose (Dol-P-Man) is a key mannosyl

143 patients were approximately 95% deficient in dolichol-phosphate-mannose (Dol-P-Man) synthase activity

144 ntified as a small stabilizer subunit of the dolichol-phosphate-mannose (DPM) synthase complex.

145 mutations in DPM2, 1 of the subunits of the dolichol-phosphate-mannose (DPM) synthase; the patient i

146 In Archaea, dolichol phosphates have been implicated as glycan carri

147 olcanii contains a series of C(55) and C(60) dolichol phosphates presenting saturated isoprene subuni

148 Dolichol plays an indispensable role in the N-glycosylat

149 5 (present in Entamoeba and Trichomonas) and dolichol-PP- and N-linked GlcNAc2 (present in Giardia) h

150 nzyme that catalyzes the reaction: GDP-Man + dolichol-PP-GlcNAc2 --> dolichol-PP-GlcNAc2-Man + GDP.

151 reaction: GDP-Man + dolichol-PP-GlcNAc2 --> dolichol-PP-GlcNAc2-Man + GDP.

152 Fourth, dolichol-PP-GlcNAc2Man5 (present in Entamoeba and Tricho

153 s (Alg) by means of a lipid-linked precursor dolichol-PP-GlcNAc2Man9Glc3.

154 ases, this inventory accurately predicts the dolichol-PP-glycans observed.

155 to characterize Alg glycosyltransferases and dolichol-PP-glycans of diverse protists, including many

156 2 and others not yet identified), which make dolichol-PP-glycans, lead to numerous congenital disorde

157 the present diversity of protist and fungal dolichol-PP-linked glycans appears to result from second

158 e alpha-isoprene unit of polyprenols to form dolichols, required for synthesis of dolichol-linked mon

159 2)-P-P-dolichol or Man(9)[(3)H]GlcNAc(2)-P-P-dolichol, respectively.

160 CPTBP in yeast and in E. coli confirmed that dolichol synthase activity strictly requires both protei

161 n by GlcNAc-1-P transferase (GPT), mannose-P-dolichol synthase, glucose-P-dolichol synthase, or LLO s

162 GPT), mannose-P-dolichol synthase, glucose-P-dolichol synthase, or LLO synthesis in vitro, as reporte

163 cis-prenyltransferase (CPT) is required for dolichol synthesis, but also point to other factor(s) th

164 S is a highly conserved essential enzyme for dolichol synthesis, permitting global N-linked glycosyla

165 zyme responsible for synthesis of GlcNAc-P-P-dolichol, the committed step of dolichol-P-P-oligosaccha

166 l) stimulated the biosynthesis of GlcNAc-P-P-dolichol; the apparent K(i) values for GlcNAc-P-P-dolich

167 ctivity in vitro and convert Man5GlcNAc2-P-P-dolichol to Glc0-3Man9GlcNAc2-P-P-dolichol in vivo.

168 dicated competitive inhibition by GlcNAc-P-P-dolichol toward the substrate UDP-GlcNAc and non-competi

169 nt N-glycans originating from Man5GlcNAc2-PP-dolichol transferred by TbSTT3A, and endoglycosidase H-s

170 ve N-glycans originating from Man9GlcNAc2-PP-dolichol transferred by TbSTT3B.

171 feed into biosynthetic pathways for sterols, dolichol, ubiquinone, heme, isopentenyl adenine, and pre

172 hosphate, an important precursor of sterols, dolichols, ubiquinones, and prenylated proteins.

173 or GlcNAc-P-P-dolichol and GlcNAc-GlcNAc-P-P-dolichol under basal conditions were 4.4 and 2.8 microM,

174 ides (LLO; glucose(3)mannose(9)GlcNAc(2)-P-P-dolichol) used for protein N-glycosylation.

175 terized, and the human Lec35 gene (mannose-P-dolichol utilization defect 1) was mapped to 17p12-13.

176 Inhibition by GlcNAc-GlcNAc-P-P-dolichol was uncompetitive toward UDP-GlcNAc and competi

177 or GlcNAc-P-P-dolichol and GlcNAc-GlcNAc-P-P-dolichol were 2.2 and 11 microM, respectively.

178 lls because statin prevents the synthesis of dolichol, which is essential for the formation of dolich

179 onstrated abundant Glc(3)Man(9)GlcNAc(2)-P-P-dolichol, without hypoglycosylation, CDG-Ia fibroblasts