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https://www.readbyqxmd.com/read/29444209/geranylgeranyl-pyrophosphate-synthase-facilitates-the-organization-of-cardiomyocytes-during-mid-gestation-through-modulating-protein-geranylgeranylation-in-mouse-heart
#1
Zhong Chen, Na Xu, Danyang Chong, Shan Guan, Chen Jiang, Zhongzhou Yang, Chaojun Li
Aims: With the maturation of placenta, ventricular chamber maturation enhances cardiac contractile performance to adapt to the metabolic demand of growing embryo. The organization of cardiomyocytes is required for the morphological remodeling in ventricular chamber maturation. However, the mechanism governing the establishment of cardiac cytoarchitecture during ventricular chamber maturation is still poorly studied. Methods and results: Here, we found that the expression of geranylgeranyl pyrophosphate synthase (Ggpps), which mediates protein geranylgeranylation, increased in the mouse heart after the onset of placental function...
February 12, 2018: Cardiovascular Research
https://www.readbyqxmd.com/read/29377583/overexpression-of-geranylgeranyl-diphosphate-synthase-contributes-to-tumour-metastasis-and-correlates-with-poor-prognosis-of-lung-adenocarcinoma
#2
Xiaoxia Wang, Wujian Xu, Ping Zhan, Tianxiang Xu, Jiajia Jin, Yingying Miu, Zejun Zhou, Qingqing Zhu, Bing Wan, Guangmin Xi, Liang Ye, Yafang Liu, Jianwei Gao, Huijuan Li, Tangfeng Lv, Yong Song
This study aimed to evaluate the biological role of geranylgeranyl diphosphate synthase (GGPPS) in the progression of lung adenocarcinoma. GGPPS expression was detected in lung adenocarcinoma tissues by qRT-PCR, tissue microarray (TMA) and western blotting. The relationships between GGPPS expression and the clinicopathological characteristics and prognosis of lung adenocarcinoma patients were assessed. GGPPS was down-regulated in SPCA-1, PC9 and A549 cells using siRNA and up-regulated in A549 cells using an adenoviral vector...
January 29, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29345110/remarkable-similarity-in-plasmodium-falciparum-and-plasmodium-vivax-geranylgeranyl-diphosphate-synthase-ggpps-dynamics-and-its-implication-for-anti-malarial-drug-design
#3
Aishwarya Venkatramani, Clarisse G Ricci, Eric Oldfield, J Andrew McCammon
Malaria, mainly caused by Plasmodium falciparum and Plasmodium vivax, has been a growing cause of morbidity and mortality. P. falciparum is more lethal than is P. vivax, but there is a vital need for effective drugs against both species. Geranylgeranyl diphosphate synthase (GGPPS) is an enzyme involved in the biosynthesis of quinones and in protein prenylation, and has been proposed to be a malaria drug target. However, the structure of P. falciparum GGPPS (PfGGPPS) has not been determined, due to difficulties in crystallization...
January 18, 2018: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29276048/specific-inhibition-of-the-bifunctional-farnesyl-geranylgeranyl-diphosphate-synthase-in-malaria-parasites-via-a-new-small-molecule-binding-site
#4
Jolyn E Gisselberg, Zachary Herrera, Lindsey M Orchard, Manuel Llinás, Ellen Yeh
The bifunctional farnesyl/geranylgeranyl diphosphate synthase (FPPS/GGPPS) is a key branchpoint enzyme in isoprenoid biosynthesis in Plasmodium falciparum (malaria) parasites. PfFPPS/GGPPS is a validated, high-priority antimalarial drug target. Unfortunately, current bisphosphonate drugs that inhibit FPPS and GGPPS enzymes by acting as a diphosphate substrate analog show poor bioavailability and selectivity for PfFPPS/GGPPS. We identified a new non-bisphosphonate compound, MMV019313, which is highly selective for PfFPPS/GGPPS and showed no activity against human FPPS or GGPPS...
December 15, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/29146946/de-novo-transcriptome-sequencing-of-meja-induced-taraxacum-koksaghyz-rodin-to-identify-genes-related-to-rubber-formation
#5
XinWen Cao, Jie Yan, JiLiang Lei, Jin Li, JianBo Zhu, HuiYan Zhang
Increase in the consumption of natural rubber (NR) has necessitated the identification of alternative sources of NR. The quality of NR produced by Taraxacum koksaghyz Rodin (TKS) is comparable to that from Hevea brasiliensis (H.brasiliensis), and therefore, TKS is being considered as an alternative source of NR. Here, we sequenced the TKS root transcriptome after wild TKS seedlings were treated with methyl jasmonate (MeJA) for 0, 6, and 24 h. The clean reads generated for each experimental line were assembled into 127,833 unigenes...
November 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28918530/exogenous-and-endogenous-increase-in-fungal-ggpp-increased-fungal-taxol-production
#6
Sameh S M Soliman, Kareem A Mosa, Ali A El-Keblawy, Mohamed I Husseiny
Taxol is an anticancer identified in both endophytic fungus and its host plant. Plant Taxol is a diterpenoid with geranylgeranyl diphosphate (GGPP) mediates the biosynthesis of its terpenoid moiety. Previous report has suggested that fungal Taxol may require terpenoid pathway for its biosynthesis. Here in this study, feeding a Taxol-producing endophytic fungus (Paraconiothyrium SSM001) with terpenoid precursors including isopentenyl pyrophosphate (IPP, isoprene) and GGPP enhanced Taxol production threefold and fivefold, respectively, compared to the control...
October 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28607067/a-recruiting-protein-of-geranylgeranyl-diphosphate-synthase-controls-metabolic-flux-toward-chlorophyll-biosynthesis-in-rice
#7
Fei Zhou, Cheng-Yuan Wang, Michael Gutensohn, Ling Jiang, Peng Zhang, Dabing Zhang, Natalia Dudareva, Shan Lu
In plants, geranylgeranyl diphosphate (GGPP) is produced by plastidic GGPP synthase (GGPPS) and serves as a precursor for vital metabolic branches, including chlorophyll, carotenoid, and gibberellin biosynthesis. However, molecular mechanisms regulating GGPP allocation among these biosynthetic pathways localized in the same subcellular compartment are largely unknown. We found that rice contains only one functionally active GGPPS, OsGGPPS1, in chloroplasts. A functionally active homodimeric enzyme composed of two OsGGPPS1 subunits is located in the stroma...
June 27, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28333111/solanesol-biosynthesis-in-plants
#8
REVIEW
Ning Yan, Yanhua Liu, Hongbo Zhang, Yongmei Du, Xinmin Liu, Zhongfeng Zhang
Solanesol is a non-cyclic terpene alcohol composed of nine isoprene units that mainly accumulates in solanaceous plants. Solanesol plays an important role in the interactions between plants and environmental factors such as pathogen infections and moderate-to-high temperatures. Additionally, it is a key intermediate for the pharmaceutical synthesis of ubiquinone-based drugs such as coenzyme Q10 and vitamin K2, and anti-cancer agent synergizers such as N-solanesyl-N,N'-bis(3,4-dimethoxybenzyl) ethylenediamine (SDB)...
March 23, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28072828/ggpp-mediated-protein-geranylgeranylation-in-oocyte-is-essential-for-the-establishment-of-oocyte-granulosa-cell-communication-and-primary-secondary-follicle-transition-in-mouse-ovary
#9
Chen Jiang, Fan Diao, Yong-Juan Sang, Na Xu, Rui-Lou Zhu, Xiu-Xing Wang, Zhong Chen, Wei-Wei Tao, Bing Yao, Hai-Xiang Sun, Xing-Xu Huang, Bin Xue, Chao-Jun Li
Folliculogenesis is a progressive and highly regulated process, which is essential to provide ova for later reproductive life, requires the bidirectional communication between the oocyte and granulosa cells. This physical connection-mediated communication conveys not only the signals from the oocyte to granulosa cells that regulate their proliferation but also metabolites from the granulosa cells to the oocyte for biosynthesis. However, the underlying mechanism of establishing this communication is largely unknown...
January 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28031082/association-between-geranylgeranyl-pyrophosphate-synthase-gene-polymorphisms-and-bone-phenotypes-and-response-to-alendronate-treatment-in-chinese-osteoporotic-women
#10
Lan-Wen Han, Dou-Dou Ma, Xiao-Jie Xu, Fang Lü, Yi Liu, Wei-Bo Xia, Yan Jiang, Ou Wang, Xiao-Ping Xing, Mei Li
Objective To investigate the relationship between geranylgeranyl pyrophosphate synthase (GGPPS) gene polymorphisms and bone response to alendronate in Chinese osteoporotic women.Methods A total of 639 postmenopausal women with osteoporosis or osteopenia were included and randomly received treatment of low dose (70 mg per two weeks) or standard dose (70 mg weekly) of alendronate for one year. The six tag single nucleotide polymorphisms of GGPPS gene were identified. Bone mineral density (BMD), serum cross-linked C-telopeptide of type I collagen (β-CTX), and total alkaline phosphatase (ALP) were measured before and after treatment...
March 20, 2016: Chinese Medical Sciences Journal, Chung-kuo i Hsüeh K'o Hsüeh Tsa Chih
https://www.readbyqxmd.com/read/27853836/increasing-the-synthesis-of-bioactive-abietane-diterpenes-in-salvia-sclarea-hairy-roots-by-elicited-transcriptional-reprogramming
#11
M C Vaccaro, A Mariaevelina, N Malafronte, N De Tommasi, A Leone
Transcriptional activation of genes belonging to the plastidial MEP-derived isoprenoid pathway by elicitation with methyl jasmonate and coronatine enhanced the content of bioactive abietane diterpenes in Salvia sclarea hairy roots. We have shown that aethiopinone, an abietane diterpene synthesized in Salvia sclarea roots is cytotoxic and induces apoptosis in human melanoma cells. To develop a production platform for this compound and other abietane diterpenes, hairy root technology was combined with the elicitation of methyl jasmonate (MeJA) or the phytotoxin coronatine (Cor)...
February 2017: Plant Cell Reports
https://www.readbyqxmd.com/read/27707890/a-single-arabidopsis-gene-encodes-two-differentially-targeted-geranylgeranyl-diphosphate-synthase-isoforms
#12
M Águila Ruiz-Sola, M Victoria Barja, David Manzano, Briardo Llorente, Bert Schipper, Jules Beekwilder, Manuel Rodriguez-Concepcion
A wide diversity of isoprenoids is produced in different plant compartments. Most groups of isoprenoids synthesized in plastids, and some produced elsewhere in the plant cell derive from geranylgeranyl diphosphate (GGPP) synthesized by GGPP synthase (GGPPS) enzymes. In Arabidopsis (Arabidopsis thaliana), five genes appear to encode GGPPS isoforms localized in plastids (two), the endoplasmic reticulum (two), and mitochondria (one). However, the loss of function of the plastid-targeted GGPPS11 isoform (referred to as G11) is sufficient to cause lethality...
November 2016: Plant Physiology
https://www.readbyqxmd.com/read/27564465/dynamic-structure-and-inhibition-of-a-malaria-drug-target-geranylgeranyl-diphosphate-synthase
#13
Clarisse G Ricci, Yi-Liang Liu, Yonghui Zhang, Yang Wang, Wei Zhu, Eric Oldfield, J Andrew McCammon
We report a molecular dynamics investigation of the structure, function, and inhibition of geranylgeranyl diphosphate synthase (GGPPS), a potential drug target, from the malaria parasite Plasmodium vivax. We discovered several GGPPS inhibitors, benzoic acids, and determined their structures crystallographically. We then used molecular dynamics simulations to investigate the dynamics of three such inhibitors and two bisphosphonate inhibitors, zoledronate and a lipophilic analogue of zoledronate, as well as the enzyme's product, GGPP...
September 13, 2016: Biochemistry
https://www.readbyqxmd.com/read/27428767/fluorescent-farnesyl-diphosphate-analogue-a-probe-to-validate-trans-prenyltransferase-inhibitors
#14
Kuo-Hsun Teng, Erh-Ting Hsu, Ying-Hsuan Chang, Sheng-Wei Lin, Po-Huang Liang
Some trans-prenyltransferases, such as long-chain C40 octaprenyl diphosphate synthase (OPPS), short-chain C15 farnesyl diphosphate synthase (FPPS), and C20 geranylgeranyl diphosphate synthase (GGPPS), are important drug targets. These enzymes catalyze chain elongation of FPP or geranyl diphosphate (GPP) through condensation reactions with isopentenyl diphosphate (IPP), forming designated numbers of trans-double bonds in the final products. To facilitate drug discovery, we report here a sensitive and reliable fluorescence-based assay for monitoring their activities in real time...
August 9, 2016: Biochemistry
https://www.readbyqxmd.com/read/27374985/alteration-of-protein-prenylation-promotes-spermatogonial-differentiation-and-exhausts-spermatogonial-stem-cells-in-newborn-mice
#15
Fan Diao, Chen Jiang, Xiu-Xing Wang, Rui-Lou Zhu, Qiang Wang, Bing Yao, Chao-Jun Li
Spermatogenesis in adulthood depends on the successful neonatal establishment of the spermatogonial stem cell (SSC) pool and gradual differentiation during puberty. The stage-dependent changes in protein prenylation in the seminiferous epithelium might be important during the first round of spermatogenesis before sexual maturation, but the mechanisms are unclear. We have previous found that altered prenylation in Sertoli cells induced spermatogonial apoptosis in the neonatal testis, resulting in adult infertility...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27106761/geranylgeranyl-diphosphate-synthase-modulates-fetal-lung-branching-morphogenesis-possibly-through-controlling-k-ras-prenylation
#16
Wen-Jun Jia, Shan Jiang, Qiao-Li Tang, Di Shen, Bin Xue, Wen Ning, Chao-Jun Li
G proteins play essential roles in regulating fetal lung development, and any defects in their expression or function (eg, activation or posttranslational modification) can lead to lung developmental malformation. Geranylgeranyl diphosphate synthase (GGPPS) can modulate protein prenylation that is required for protein membrane-anchoring and activation. Here, we report that GGPPS regulates fetal lung branching morphogenesis possibly through controlling K-Ras prenylation during fetal lung development. GGPPS was continuously expressed in lung epithelium throughout whole fetal lung development...
June 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/26795152/molecular-cloning-functional-characterization-and-expression-of-potato-solanum-tuberosum-1-deoxy-d-xylulose-5-phosphate-synthase-1-stdxs1-in-response-to-phytophthora-infestans
#17
Maria Antonia Henriquez, Atta Soliman, Genyi Li, Abdelali Hannoufa, Belay T Ayele, Fouad Daayf
1-Deoxy-D-xylulose 5-phosphate synthase (DXS) catalyzes the initial step of the plastidial 2C-methyl-D-erythritol-4-phosphate (DOXP-MEP) pathway involved in isoprenoid biosynthesis. In this study, we cloned the complete cDNA of potato DXS gene that was designated StDXS1. StDXS1 cDNA encodes for 719 amino acid residues, with MW of 77.8 kDa, and is present in one copy in the potato genome. Phylogenetic analysis and protein sequence alignments assigned StDXS1 to a group with DXS homologues from closely related species and exhibited homodomain identity with known DXS proteins from other plant species...
February 2016: Plant Science: An International Journal of Experimental Plant Biology
https://www.readbyqxmd.com/read/26688062/single-target-high-throughput-transcription-analyses-reveal-high-levels-of-alternative-splicing-present-in-the-fpps-ggpps-from-plasmodium-falciparum
#18
Heloisa B Gabriel, Mauro F de Azevedo, Giuseppe Palmisano, Gerhard Wunderlich, Emília A Kimura, Alejandro M Katzin, João M P Alves
Malaria is a tropical disease with significant morbidity and mortality. A better understanding of the metabolism of its most important etiological agent, Plasmodium falciparum, is paramount to the development of better treatment and other mitigation measures. Farnesyldiphosphate synthase/geranylgeranyldiphosphate synthase (FPPS/GGPPS) is a key enzyme in the synthesis of isoprenic chains present in many essential structures. In P. falciparum, as well as a handful of other organisms, FPPS/GGPPS has been shown to be a bifunctional enzyme...
December 21, 2015: Scientific Reports
https://www.readbyqxmd.com/read/26575346/a-lack-of-glue-misplaces-rab27a-to-cause-islet-dysfunction-in-diabetes
#19
Anjaneyulu Kowluru
Glucose-stimulated insulin secretion (GSIS) involves interplay between metabolic and cationic events. Several lines of evidence suggest novel regulatory roles for small G proteins (Rac1, Cdc42, Rab27A) in cytoskeletal remodelling and docking of insulin granules on the plasma membrane for insulin secretion. Emerging evidence implicates novel roles for post-translational prenylation (farnesylation and geranylgeranylation) of G proteins for their targeting to appropriate membranous compartments. While several recent studies were focused on prenylating enzymes in the islet β-cell, a significant knowledge gap exists on the regulatory roles and function of enzymes that mediate intracellular generation of prenyl pyrophosphate substrates (farnesyl and geranylgeranyl pyrophosphates) for prenyltransferases...
February 2016: Journal of Pathology
https://www.readbyqxmd.com/read/26552162/-cloning-and-expression-analysis-of-ggpps-gene-from-panax-notoginseng
#20
Dan-dan Min, Mei-qiong Tang, Gang Li, Xiao-sheng Qu, Jian-hua Miao
According to the transcriptome dataset of Panax notoginseng, the key geranylgeranyl pyrophosphate synthase gene (GGPPS) in terpenoid backbone biosynthesis was selected to be cloned. Using specific primer pairs combining with RACE (rapid amplification of cDNA ends) technique, the full-length cDNA sequence with 1 203 bp, which containing a 1 035 bp open reading frame, was cloned and named as PnGGPPS. The corresponding full-length DNA sequence contained 2 370 bp, consisted of 1 intron and 2 exons. The deduced protein PnGGPPS contained 344 amino acids and shared more than 73% identity with GGPPS from Ricinus communis and Salvia miltiorrhiza...
June 2015: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
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