ライフサイエンスコーパス: GGPP

1 GGPP is a pivotal metabolite downstream of PCSK9 by acti

2 GGPP is then proposed to condense with tryptophan to for

3 GGPP shortage abolishes normal membrane localization and

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

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

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

7 GGPP-dependent misfolding was still extant but occurred

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

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

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

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

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

13 l-GCIIL and an uncompetitive pattern against GGPP.

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

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

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

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

18 induces cholesterol de novo biosynthesis and GGPP accumulation.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

33 ssess agonist properties relative to FPP and GGPP.

34 nd downstream isoprenoids, including FPP and GGPP.

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

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

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

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

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

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

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

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

43 Both GGPP formation and phytoene desaturation were elevated i

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

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

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

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

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

49 (GGPP), a prenyl diphosphate synthesized by GGPP synthase (GGPS), represents a metabolic hub for the

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

51 PYGG converted GGPP to phytoene almost quantitatively in vitro and did

52 hosphate, and a cyclase domain that converts GGPP into fusicoccadiene, a precursor of the diterpene g

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

54 rast, PSY could not access freely diffusible GGPP or time-displaced GGPP supply via GGPS11, presumabl

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

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

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

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

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

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

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

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

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

64 n that generates geranylgeranyl diphosphate (GGPP) from dimethylallyl diphosphate and three equivalen

65 (AriE) cyclizes geranylgeranyl diphosphate (GGPP) into a 6/10-fused bicyclic cis-eunicellane skeleto

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

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

68 0 locus of bound geranylgeranyl diphosphate (GGPP) is in close proximity to residues from the beta-su

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

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

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

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

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

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

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

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

77 Geranylgeranyl diphosphate (GGPP), a prenyl diphosphate synthesized by GGPP synthase

78 that decrease of geranylgeranyl diphosphate (GGPP), an intermediate metabolite in the mevalonate path

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

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

81 ded with (E,E,E)-geranylgeranyl diphosphate (GGPP), LlTPS gave sobralene as its major product.

82 rs to form C(20) geranylgeranyl diphosphate (GGPP), which is then converted into a polycyclic product

83 ied by increased geranylgeranyl diphosphate (GGPP)-a metabolite necessary for KRAS activation.

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

85 carbon moiety in geranylgeranyl diphosphate (GGPP).

86 conformation of geranylgeranyl diphosphate (GGPP).

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

88 ess freely diffusible GGPP or time-displaced GGPP supply via GGPS11, presumably due to liposomal sequ

89 GDPS), which generates the isoprenoid donor (GGPP), as anti-Rab agents.

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

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

92 metabolite channeling and/or competition for GGPP among enzymes that function in independent branches

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

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

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

96 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

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

98 e PT and cyclase domains is not required for GGPP channeling, although covalent linkage may improve c

99 lying that the SSD is not a binding site for GGPP.

100 251 cells which were reversed with MEV, FPP, GGPP.

101 casbenes, taxenes, and others originate from GGPP.

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

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

104 Furthermore, GGPP-dependent protein modifications control signaling t

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

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

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

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

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

110 -[1-(2)H]farnesyl diphosphate or (S)-[1-(2)H]GGPP.

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

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

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

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

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

116 This suggests insufficient GGPP substrate availability for chlorophyll biosynthesis

117 ontrolled by the sterol pathway intermediate GGPP, which causes misfolding of Hmg2, leading to degrad

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

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

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

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

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

123 Moreover, GGPP competition experiments with other diterpene cyclas

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

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

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

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

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

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

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

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

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

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

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

135 tPA production from the inhibitory effect of GGPP.

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

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

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

139 2 and required for mallosteric misfolding of GGPP as studied by in vitro limited proteolysis.

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

141 n interactions and the amphipathic nature of GGPP suggest metabolite channeling and/or competition fo

142 facilitates a physiologically useful rate of GGPP response and implying that the SSD is not a binding

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

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

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

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

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

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

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

150 Either FPP or GGPP completely prevents lovastatin-induced upregulation

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

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

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

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

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

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

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

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

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

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

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

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

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

164 c intermediate geranylgeranyl pyrophosphate (GGPP) is required to specifically drive IL-10 production

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

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

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

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

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

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

171 ol isoprenoid, geranylgeranyl pyrophosphate (GGPP).

172 way leading to geranylgeranyl pyrophosphate (GGPP).

173 iate precursor geranylgeranyl pyrophosphate (GGPP).

174 enoids such as geranylgeranyl pyrophosphate (GGPP).

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

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

177 ived isoprene gernanylgeranyl pyrophosphate (GGPP).

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

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

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

181 is via PSY strictly depended on simultaneous GGPP supply via GGPS11.

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

183 Surprisingly, GGPP is not channeled intramolecularly from the prenyltr

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

185 are functional proteins that can synthesize GGPP.

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

187 Finally, we have found that GGPP-regulated misfolding occurred in detergent-solubili

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

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

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

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

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

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

194 is operative in catalysis since most of the GGPP generated by the PT remains on the enzyme for cycli

195 quantitatively in vitro and did not show the GGPP leakage typical of the individual enzymes.

196 or chlorophyll biosynthesis achieved through GGPP flux redirection to carotenogenesis.

197 rminal sequence affected the ratio of FPP to GGPP.

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

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

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

201 lator PCSK9 promotes APC/KRAS-mutant CRC via GGPP-KRAS/MEK/ERK axis and is a therapeutic target.

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

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

204 thase (GGPPS) acts as a hub to interact with GGPP-utilizing enzymes for the synthesis of specific dow

205 Moreover, metabolic supplementation with GGPP is able to reverse this defect.

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

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