ライフサイエンスコーパス: GGPP

1 GGPP is then proposed to condense with tryptophan to for

2 GGPP synthase catalyzes the synthesis of all-trans-geran

3 GGPP synthase mRNA expression was increased 5- to 20-fol

4 GGPP-caused Hmg2p degradation met all the criteria for t

5 Incubation of (R)-[4-(2H1)]GGPP (17) with the recombinant enzyme gave a 10:10:80 mi

6 synthase activity was not detected when [3H]GGPP was used as the substrate.

7 nt of (E,E,E)-geranylgeranyl diphosphate (8, GGPP) to a mixture of abietadiene (1a), double bond isom

8 erized a bifunctional GPP/FPP synthase and a GGPP synthase in the mountain pine beetle.

9 The action of added GGPP did not require production of endogenous sterol mol

10 l-GCIIL and an uncompetitive pattern against GGPP.

11 Lowering lanosterol in the cell allowed GGPP-stimulated Hmg2 ERAD.

12 the enzyme and several isoprenoid analogues, GGPP, and the farnesylated peptide product using a combi

13 liana; rAtCPS) demonstrating that Mg(2+) and GGPP exert synergistic substrate inhibition effects on C

14 and GGPP, and competitive binding of ATP and GGPP.

15 s of FPP (0.125+/-0.010 pmol/10(6)cells) and GGPP (0.145+/-0.008 pmol/10(6)cells) in NIH3T3 cells.

16 ivity and the endogenous isoprenoids FPP and GGPP also raised Abeta42.

17 ed these maize enzymes produced both FPP and GGPP and that the N-terminal sequence affected the ratio

18 The respective concentrations of FPP and GGPP are as follows: 0.355+/-0.030 and 0.827+/-0.082 uni

19 s method allows for determination of FPP and GGPP concentrations in any tissue type and is sensitive

20 ped a method to isolate and quantify FPP and GGPP from mammalian tissues.

21 termination of the concentrations of FPP and GGPP in any cell type or tissue.

22 provide evidence for direct roles of FPP and GGPP in regulating transcriptional and post-transcriptio

23 Furthermore, changes in FPP and GGPP levels following treatment of cells with isoprenoid

24 lyisoprenoid diphosphates, including FPP and GGPP over a variety of glycerol- and sphingo-phospholipi

25 FPP and GGPP were isolated by a combined homogenization and extr

26 FPP and GGPP were quantified by high-performance liquid chromato

27 I (GGTase I) were used to conjugate FPP and GGPP with fluorescent dansylated peptides.

28 r isoprenoid diphosphate substrates, FPP and GGPP, respectively.

29 ssess agonist properties relative to FPP and GGPP.

30 nd downstream isoprenoids, including FPP and GGPP.

31 esponding synthases (FPP synthase [FPPS] and GGPP synthase [GGPPS]) catalyze, respectively, the addit

32 enzyme exhibiting altered ratios of GPP and GGPP synthase activities and greatly enhanced catalytic

33 dulate IPP flux distribution between GPP and GGPP synthesis in planta.

34 ctions: competitive binding of inhibitor and GGPP, and competitive binding of ATP and GGPP.

35 in was completely reversed by mevalonate and GGPP, but not by FPP.

36 gnificant inhibition of activity was seen at GGPP concentrations above 100 microM.

37 present study it is shown that PGGT-I binds GGPP 330-fold tighter than FPP and that PFT binds FPP 15

38 -nucleophilicity at the delta10 double bond (GGPP numbering) was synthesized and incubated with taxad

39 Both GGPP formation and phytoene desaturation were elevated i

40 Therefore, in vivo, where both GGPP and FPP compete for the binding to prenyltransferas

41 (GGPP) mediates proliferation, whereas both GGPP and its precursor, farnesyl-PP, regulate the Th1 di

42 A in Tsc2-/- cells, and this was reversed by GGPP.

43 T cell expansion, which could be skipped by GGPP supplementation.

44 nylgeranyl diphosphate (GGPP) synthesized by GGPP synthase (GGPPS) enzymes.

45 photosynthetic pigments through their common GGPP precursor is dramatically increased.

46 because none of its downstream derivatives, GGPP, ubiquinone, or cholesterol, were effective.

47 etween the C(20) geranylgeranyl diphosphate (GGPP) and a protein-derived thiol to form a thioether li

48 in length using geranylgeranyl diphosphate (GGPP) and isopentenyl diphosphate as substrates.

49 sphate (FPP) and geranylgeranyl diphosphate (GGPP) are branch point intermediates of isoprenoid biosy

50 sphate (FPP) and geranylgeranyl diphosphate (GGPP) are intermediates in the synthesis of cholesterol

51 sphate (FPP) and geranylgeranyl diphosphate (GGPP) are precursors to many isoprenoids having essentia

52 y identifies C20 geranylgeranyl diphosphate (GGPP) as a precursor for lycopaoctaene biosynthesis, the

53 isomerization of geranylgeranyl diphosphate (GGPP) by diterpene synthases (diTPSs).

54 monoterpene and geranylgeranyl diphosphate (GGPP) diversities, and plant morphology by transient exp

55 diphosphate, and geranylgeranyl diphosphate (GGPP) from dimethylallyl diphosphate and isopentenyl dip

56 sm that converts geranylgeranyl diphosphate (GGPP) into labda-7,13E-dienyl diphosphate as verified by

57 Geranylgeranyl diphosphate (GGPP) is a key precursor of various isoprenoids that hav

58 0 locus of bound geranylgeranyl diphosphate (GGPP) is in close proximity to residues from the beta-su

59 iphosphate (FPP)/geranylgeranyl diphosphate (GGPP) synthase (TgFPPS) that synthesizes C(15) and C(20)

60 cell derive from geranylgeranyl diphosphate (GGPP) synthesized by GGPP synthase (GGPPS) enzymes.

61 renoid substrate geranylgeranyl diphosphate (GGPP) to form taxa-4(5),11(12)diene, which is catalysed

62 two molecules of geranylgeranyl diphosphate (GGPP) to give prephytoene diphosphate (PPPP) and the sub

63 hate [(S)-GP] by geranylgeranyl diphosphate (GGPP) to produce (S)-geranylgeranylglyceryl phosphate [(

64 ation of (E,E,E)-geranylgeranyl diphosphate (GGPP) to taxa-4(5),11(12)-diene (Scheme 1, 5 --> 2) as t

65 P), or 20-carbon geranylgeranyl diphosphate (GGPP) via a dioxygenase- or cytochrome P450-mediated car

66 phate (FPP), and geranylgeranyl diphosphate (GGPP) were synthesized.

67 sis of all-trans-geranylgeranyl diphosphate (GGPP), an isoprenoid used for protein isoprenylation in

68 strate, (E,E,E,)-geranylgeranyl diphosphate (GGPP), is also a direct precursor of carotenoids and the

69 lorin ring and a geranylgeranyl diphosphate (GGPP)-derived isoprenoid, which are generated by the tet

70 conformation of geranylgeranyl diphosphate (GGPP).

71 carbon moiety in geranylgeranyl diphosphate (GGPP).

72 ation of (E,E,E)-geranylgeranyl diphosphate (GGPP, 7) to taxadiene (5) is proposed to proceed through

73 Manipulation of endogenous GGPP by several means showed that naturally made GGPP co

74 and GGTase-I:GGPP complexes show 1:1 (enzyme:GGPP) stoichiometry.

75 Michaelis constants for GGPP and Ypt1p were 1.6 and 1.1 microM, respectively; Vm

76 E)-geranylgeraniol, a dead-end inhibitor for GGPP, gave a competitive double reciprocal plot for vari

77 were conducted with dead-end inhibitors for GGPP and the peptide substrate.

78 01 s(-1), K(M)(G) = 0.86 +/- 0.05 microM for GGPP, and K(M)(D) = 1.6 +/- 0.1 microM for dansyl-GCIIL

79 Three mRNAs for GGPP synthase of 4.3, 3.2, and 1.7 kb were detected in N

80 251 cells which were reversed with MEV, FPP, GGPP.

81 casbenes, taxenes, and others originate from GGPP.

82 ble RabGGTase:GG pyrophosphate (GGPP), FTase:GGPP, and GGTase-I:GGPP complexes show 1:1 (enzyme:GGPP)

83 otein) fusion proteins of the ten functional GGPP synthases localized to plastids, mitochondria and t

84 phate (FPP) and geranylgeranylpyrophosphate (GGPP) significantly reverse atorvastatin-induced inhibit

85 phate (FPP) and geranylgeranylpyrophosphate (GGPP), respectively.

86 ate metabolites geranylgeranylpyrophosphate (GGPP) and farnesylpyrophosphate (FPP) used in the prenyl

87 e (200 microM), geranylgeranylpyrophosphate (GGPP, 1-10 microM), farnesylpyrophosphate (FPP, 5-10 mic

88 Potential binding geometries of FPP, GPP, GGPP, and analogues 1a-e were examined by modeling the m

89 -[1-(2)H]farnesyl diphosphate or (S)-[1-(2)H]GGPP.

90 rophosphate (GGPP), FTase:GGPP, and GGTase-I:GGPP complexes show 1:1 (enzyme:GGPP) stoichiometry.

91 e isoprenyl diphosphate synthases identified GGPP synthase as having the largest effect on frontalin

92 inhibition is lethal because a reduction in GGPP availability results in a stoichiometric imbalance

93 f 3T3-L1 fibroblasts into adipocytes induced GGPP synthase expression more than 20-fold.

94 g1 promotes Hmg2 stabilization by inhibiting GGPP-stimulated ERAD.

95 ed on the role of geranylgeranyl isoprenoids GGPP and geranylgeraniol (GGOH) in regulating Abeta prod

96 adation is controlled by a two-signal logic; GGPP promotes degradation, and lanosterol inhibits degra

97 K(m)((S)-GP) = 13.5 +/- 1.0 microM, and K(m)(GGPP) = 506 +/- 47 nM.

98 by several means showed that naturally made GGPP controls Hmg2p stability.

99 recipitated protein, we found that mammalian GGPP synthase synthesizes not only GGPP but also its met

100 gnificantly reversed by the addition of MVA, GGPP, and FPP.

101 d converted (+)-copalyl diphosphate, but not GGPP, into isopimaradiene and pimaradiene as major produ

102 It follows that C-1 of GGPP underwent inversion of configuration, that the A ri

103 Analysis of the action of GGPP indicated that the molecule works upstream of retro

104 s that catalyze the initial bicyclization of GGPP followed by rearrangement of a (+)-copalyl diphosph

105 The concentration of GGPP needed for half-maximal activity was approximately

106 reciprocal plot for varied concentrations of GGPP and induced potent substrate inhibition by dansyl-G

107 The cyclization of GGPP to taxadiene, catalyzed by taxadiene synthase, has

108 ion is an intermediate in the cyclization of GGPP to taxadiene.

109 n of Rho family prenylation and depletion of GGPP, in a variety of different human cancer cell lines.

110 This effect of GGPP was not recapitulated by FPP, GGOH, or related isop

111 tPA production from the inhibitory effect of GGPP.

112 Thus, the expression of GGPP synthase is regulated in multiple tissues in obesit

113 Our data show that the inhibition of GGPP synthesis by statins plays an important role in sta

114 (1) plastidial AtCPT7 extends the length of GGPP to approximately 55 carbons, which then accumulate

115 nvolved in binding the diphosphate moiety of GGPP and identified DxxxxE as a potential Mg(2+)-binding

116 evisiae or with the corresponding regions of GGPP synthases from Homo sapiens or S. cerevisiae.

117 Moreover, repletion of GGPP, which prevented acute zoledronate toxicity, and su

118 A set of GGPP analogues with abolished or perturbed pi-nucleophil

119 rescued by cholesterol, but was dependent on GGPP- and FPP-depletion.

120 mammalian GGPP synthase synthesizes not only GGPP but also its metabolic precursor farnesyl diphospha

121 e lower limit of detection is 5 pg of FPP or GGPP ( approximately 0.01 pmol).

122 ferases and other enzymes that employ FPP or GGPP as their substrates.

123 Either FPP or GGPP completely prevents lovastatin-induced upregulation

124 nsferase I are performed to conjugate FPP or GGPP to dansylated peptides.

125 ed proteins which can be prevented by FPP or GGPP, independent of restoration of protein isoprenylati

126 Co-treatment with L-mevalonate or GGPP, but not FPP or LDL, reversed mevastatin's effects.

127 anyl protein transferase I, FPP synthase, or GGPP synthase.

128 A subset of very potent GGPP-competitive inhibitors displayed slow tight binding

129 GGPPS12 (At4g38460) did not produce GGPP in E. coli.

130 tional plastid import sequence that produces GGPP for the major groups of photosynthesis-related plas

131 rn suggest subfunctionalization in providing GGPP to specific tissues, developmental stages, or metab

132 yl groups from geranylgeranyl pyrophosphate (GGPP) and farnesyl pyrophosphate (FPP) to their protein

133 hate (FPP) and geranylgeranyl pyrophosphate (GGPP) are synthetic precursors for numerous molecules es

134 an FPP whereas geranylgeranyl pyrophosphate (GGPP) does not transfer at all.

135 hate (FPP) and geranylgeranyl pyrophosphate (GGPP) in cultured cells.

136 arbon molecule geranylgeranyl pyrophosphate (GGPP) is a potent endogenous regulator of Hmg2p degradat

137 gulation while geranylgeranyl pyrophosphate (GGPP) restores Rap1a processing and prevents RhoA and Rh

138 of mevalonate, geranylgeranyl pyrophosphate (GGPP), and farnesyl pyrophosphate (FPP), which are lipid

139 PP) but not by geranylgeranyl pyrophosphate (GGPP), implicating perturbations in farnesylation rather

140 mpetitive with geranylgeranyl pyrophosphate (GGPP), rather than with the peptide substrate, which had

141 hate (FPP) and geranylgeranyl pyrophosphate (GGPP), which are used for protein prenylation, including

142 m depletion of geranylgeranyl pyrophosphate (GGPP), which is required for protein prenylation, caused

143 way leading to geranylgeranyl pyrophosphate (GGPP).

144 iate precursor geranylgeranyl pyrophosphate (GGPP).

145 enoids such as geranylgeranyl pyrophosphate (GGPP).

146 ol isoprenoid, geranylgeranyl pyrophosphate (GGPP).

147 alonate (MVA), geranylgeranyl-pyrophosphate (GGPP) and farnesyl-pyrophosphate (FPP), all intermediate

148 the isoprenoid geranylgeranyl-pyrophosphate (GGPP) mediates proliferation, whereas both GGPP and its

149 ived isoprene gernanylgeranyl pyrophosphate (GGPP).

150 Stable RabGGTase:GG pyrophosphate (GGPP), FTase:GGPP, and GGTase-I:GGPP complexes show 1:1

151 hate [FPP] and geranylgeranyl pyrophosphate [GGPP]).

152 rnover reactions by using isolated RabGGTase:GGPP complex revealed that Rab is mono-geranylgeranylate

153 cyclase, which binds and activates substrate GGPP with a three-metal ion cluster.

154 e mouse geranylgeranyl diphosphate synthase (GGPP synthase) based on its homology to proteins cloned

155 are functional proteins that can synthesize GGPP.

156 and that PFT binds FPP 15-fold tighter than GGPP.

157 Modeling also indicated that GGPP adopts a different conformation than the farnesyl c

158 launched by the unexpected observation that GGPP addition directly to living yeast cultures caused h

159 We propose that GGPP is the FPP-derived regulator of Hmg2p ubiquitinatio

160 rious tissues and life stages suggested that GGPP rather than GPP or FPP is used as a precursor to fr

161 sed an increase in the apparent K(d) for the GGPP-GGPTase I interaction from 20 pm to 4 nm, resulting

162 Comparison of the GGPP binding mode with the binding of the farnesylated p

163 rminal sequence affected the ratio of FPP to GGPP.

164 nd PFT will likely be bound predominantly to GGPP and FPP, respectively.

165 compartments for the synthesis of ubiquitous GGPP-derived isoprenoid species.

166 id hydrocarbons, but almost exclusively uses GGPP in vivo.

167 rdered binding mechanism for PGGTase-I where GGPP adds before peptide.

168 In contrast, GGTI-298 enhanced, while GGPP inhibited, MMP-1 secretion.

169 of which were reversed by co-treatment with GGPP but not FPP.

170 ociation constant (K(D)) for the PGGTase-I x GGPP complex was 120 +/- 20 nM.