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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
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
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)...
November 16, 2016: Plant Cell Reports
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 thaliana, 5 genes appear to encode GGPPS isoforms localized in plastids (2), the endoplasmic reticulum (2), and mitochondria (1). However, the loss of function of the plastid-targeted GGPPS11 isoform (referred to as G11) is sufficient to cause lethality...
October 5, 2016: Plant Physiology
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
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
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
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
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
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
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
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
Marc J C Fischer, Camille Rustenhloz, Véronique Leh-Louis, Guy Perrière
BACKGROUND: Terpenes represent one of the largest and most diversified families of natural compounds and are used in numerous industrial applications. Terpene synthase (TPS) genes originated in bacteria as diterpene synthase (di-TPS) genes. They are also found in plant and fungal genomes. The recent availability of a large number of fungal genomes represents an opportunity to investigate how genes involved in diterpene synthesis were acquired by fungi, and to assess the consequences of this process on the fungal metabolism...
2015: BMC Microbiology
Meng Zhang, Ping Su, Yong-Jin Zhou, Xiu-Juan Wang, Yu-Jun Zhao, Yu-Jia Liu, Yu-Ru Tong, Tian-Yuan Hu, Lu-Qi Huang, Wei Gao
We found triptolide synthesis is correlated with the expressions of TwGGPPS1 and TwGGPPS4 . This lays the foundation for future studies of biosynthetic pathways for triptolide and other diterpenoids in T. wilfordii. Tripterygium wilfordii is a traditional Chinese medical plant commonly used to treat rheumatoid arthritis. One of its main bioactive compounds is triptolide, which is identified as an abietane-type diterpenoid natural product. Geranylgeranyl diphosphate synthase (GGPPS) catalyses the synthesis of GGPP (geranylgeranyl diphosphate), the common precursor of diterpenes, and is therefore a crucial enzyme in diterpene biosynthesis...
December 2015: Plant Cell Reports
Shan Jiang, Di Shen, Wen-Jun Jia, Xiao Han, Ning Shen, Weiwei Tao, Xiang Gao, Bin Xue, Chao-Jun Li
Loss of first-phase insulin secretion associated with β cell dysfunction is an independent predictor of type 2 diabetes mellitus (T2DM) onset. Here we found that a critical enzyme involved in protein prenylation, geranylgeranyl pyrophosphate synthase (GGPPS), is required to maintain first-phase insulin secretion. GGPPS shows a biphasic expression pattern in islets of db/db mice during the progression of T2DM: GGPPS is increased during the insulin compensatory period, followed by a decrease during β cell dysfunction...
January 2016: Journal of Pathology
Min Kyung Kong, Hyun-Jun Kang, Jin Ho Kim, Soon Hwan Oh, Pyung Cheon Lee
The ent-kaurene is a dedicated precursor pool and is responsible for synthesizing natural sweeteners such as steviol glycosides. In this study, to produce ent-kaurene in Escherichia coli, we modularly constructed and expressed two ent-kaurene genes encoding ent-copalyl diphosphate synthase (CPPS) and ent-kaurene synthase (KS) from Stevia rebaudiana known as a typical plant producing steviol glycoside. The CPPS and KS from S. rebaudiana were functionally expressed in a heterologous host E. coli. Furthermore, in order to enhance ent-kaurene production in E...
November 20, 2015: Journal of Biotechnology
Meng Zhang, Ping Su, Yu-jia Liu, Yu-ru Tong, Yu-jun Zhao, Wei Gao, Xiu-juan Wang, Lu-qi Huang
A full-length cDNA of GGPPS gene from Tripterygium wilfordii suspension cells was obtained by use of RACE strategy (GeneBank: KM978333), and then analyzed by bioinformatics approaches. TwGGPPS cDNA has 1857 nucleotides and an open reading frame (ORF) encoding a protein of 514 amino acid residues. The deduced protein has isoelectric point (pI) of 7.85, a calculated molecular weight about 57.13 kD, 5 conserved domains and 2 functional domains. PSORT Prediction showed it was located at plasma membrane. Phylogenetic analysis demonstrated that TwGGPPS1 was similar to GGPPS from other species of plants...
March 2015: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
M Águila Ruiz-Sola, Diana Coman, Gilles Beck, M Victoria Barja, Maite Colinas, Alexander Graf, Ralf Welsch, Philipp Rütimann, Peter Bühlmann, Laurent Bigler, Wilhelm Gruissem, Manuel Rodríguez-Concepción, Eva Vranová
Most plastid isoprenoids, including photosynthesis-related metabolites such as carotenoids and the side chain of chlorophylls, tocopherols (vitamin E), phylloquinones (vitamin K), and plastoquinones, derive from geranylgeranyl diphosphate (GGPP) synthesized by GGPP synthase (GGPPS) enzymes. Seven out of 10 functional GGPPS isozymes in Arabidopsis thaliana reside in plastids. We aimed to address the function of different GGPPS paralogues for plastid isoprenoid biosynthesis. We constructed a gene co-expression network (GCN) using GGPPS paralogues as guide genes and genes from the upstream and downstream pathways as query genes...
January 2016: New Phytologist
Linfeng You, Haixing Yang, Junfang Lin, Zhiwei Ye, Liqiong Guo, Yanhua Xin
Taxa-4(5),11(12)-diene is the precursor for paclitaxel biosynthesis. The diterpenoid paclitaxel (marketed as Taxol), a plant secondary metabolite isolated from yew, is an effective drug widely used in the treatment of numerous cancers. However, further application of taxol has been restricted due to its low yield in plants and the difficulties in extraction. To increase the intact isoprene flux, we constructed the fusion gene plasmid pBgGGTS and individual cassette plasmid pBgGGgTS to enhance the expression levels of geranylgeranyl diphosphate synthase gene (ggpps) and a taxadiene synthase gene (ts) in Coprinopsis cinerea...
March 2015: Sheng Wu Gong Cheng Xue Bao, Chinese Journal of Biotechnology
Weiwei Tao, Jing Wu, Bing-Xian Xie, Yuan-Yuan Zhao, Ning Shen, Shan Jiang, Xiu-Xing Wang, Na Xu, Chen Jiang, Shuai Chen, Xiang Gao, Bin Xue, Chao-Jun Li
Elevated circulating free fatty acid levels are important contributors to insulin resistance in the muscle and liver, but the underlying mechanisms require further elucidation. Here, we show that geranylgeranyl diphosphate synthase 1 (GGPPS), which is a branch point enzyme in the mevalonic acid pathway, promotes lipid-induced muscle insulin resistance through activation of the RhoA/Rho kinase signaling pathway. We have found that metabolic perturbation would increase GGPPS expression in the skeletal muscles of db/db mice and high fat diet-fed mice...
August 14, 2015: Journal of Biological Chemistry
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