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Farnesylation

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https://www.readbyqxmd.com/read/28921701/an-exception-among-diatoms-unique-organization-of-genes-involved-in-isoprenoid-biosynthesis-in-rhizosolenia-setigera-ccmp-1694
#1
Victor Marco Emmanuel N Ferriols, Ryoko Yaginuma-Suzuki, Kazunari Fukunaga, Takashi Kadono, Masao Adachi, Shigeki Matsunaga, Shigeru Okada
The marine diatom Rhizosolenia setigera is unique among this group of microalgae given that it is one of only a handful of diatom species that can produce highly branched isoprenoid (HBI) hydrocarbons. In our efforts to determine distinguishing molecular characteristics in R. setigera CCMP 1694 that could help elucidate the underlying mechanisms for its ability to biosynthesize HBIs, we discovered the occurrence of independent genes encoding for two isopentenyl diphosphate isomerases (RsIDI1 and RsIDI2) and one squalene synthase (RsSQS), enzymes that catalyze non-consecutive steps in isoprenoid biosynthesis...
September 15, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28910323/comparative-proteomic-analyses-reveal-the-proteome-response-to-short-term-drought-in-italian-ryegrass-lolium-multiflorum
#2
Ling Pan, Zhongfu Yang, Jianping Wang, Pengxi Wang, Xiao Ma, Meiliang Zhou, Ji Li, Nie Gang, Guangyan Feng, Junming Zhao, Xinquan Zhang
Drought is a major abiotic stress that impairs growth and productivity of Italian ryegrass. Comparative analysis of drought responsive proteins will provide insight into molecular mechanism in Lolium multiflorum drought tolerance. Using the iTRAQ-based approach, proteomic changes in tolerant and susceptible lines were examined in response to drought condition. A total of 950 differentially accumulated proteins was found to be involved in carbohydrate metabolism, amino acid metabolism, biosynthesis of secondary metabolites, and signal transduction pathway, such as β-D-xylosidase, β-D-glucan glucohydrolase, glycerate dehydrogenase, Cobalamin-independent methionine synthase, glutamine synthetase 1a, Farnesyl pyrophosphate synthase, diacylglycerol, and inositol 1, 4, 5-trisphosphate, which might contributed to enhance drought tolerance or adaption in Lolium multiflorum...
2017: PloS One
https://www.readbyqxmd.com/read/28904410/recent-advances-in-ergosterol-biosynthesis-and-regulation-mechanisms-in-saccharomyces-cerevisiae
#3
REVIEW
Zhihong Hu, Bin He, Long Ma, Yunlong Sun, Yali Niu, Bin Zeng
Ergosterol, an important component of the fungal cell membrane, is not only essential for fungal growth and development but also very important for adaptation to stress in fungi. Ergosterol is also a direct precursor for steroid drugs. The biosynthesis of ergosterol can be divided into three modules: mevalonate, farnesyl pyrophosphate (farnesyl-PP) and ergosterol biosynthesis. The regulation of ergosterol content is mainly achieved by feedback regulation of ergosterol synthase activity through transcription, translation and posttranslational modification...
September 2017: Indian Journal of Microbiology
https://www.readbyqxmd.com/read/28898524/enzymatic-addition-of-alcohols-to-terpenes-by-squalene-hopene-cyclase-variants
#4
Lisa C Kühnel, Bettina M Nestl, Bernhard Hauer
Squalene hopene cyclases (SHC) catalyze the polycyclization of squalene into a mixture of hopene and hopanol. Recently, amino acid residues lining the catalytic cavity of the SHC from Alicyclobacillus acidocaldarius were replaced by small and large hydrophobic amino acids. The alteration of leucine 607 to phenylalanine resulted in increased enzymatic activity towards the formation of an intermolecular farnesyl-farnesyl ether product from farnesol. Furthermore, the addition of small chain alcohols acting as nucleophiles led to the formation of non-natural ether-linked terpenoids and thus, to a significant alteration of the product pattern compared to wildtype...
September 12, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28885709/prenylation-of-viral-proteins-by-enzymes-of-the-host-virus-driven-rationale-for-therapy-with-statins-and-ft-ggt1-inhibitors
#5
REVIEW
Ekaterina S Marakasova, Birgit Eisenhaber, Sebastian Maurer-Stroh, Frank Eisenhaber, Ancha Baranova
Intracellular bacteria were recently shown to employ eukaryotic prenylation system for modifying activity and ensuring proper intracellular localization of their own proteins. Following the same logic, the proteins of viruses may also serve as prenylation substrates. Using extensively validated high-confidence prenylation predictions by PrePS with a cut-off for experimentally confirmed farnesylation of hepatitis delta virus antigen, we compiled in silico evidence for several new prenylation candidates, including IRL9 (CMV) and few other proteins encoded by Herpesviridae, Nef (HIV-1), E1A (human adenovirus 1), NS5A (HCV), PB2 (influenza), HN (human parainfluenza virus 3), L83L (African swine fever), MC155R (molluscum contagiosum virus), other Poxviridae proteins, and some bacteriophages of human associated bacteria...
September 8, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28880478/role-of-g-proteins-in-islet-function-in-health-and-diabetes
#6
REVIEW
Anjaneyulu Kowluru
Glucose-stimulated insulin secretion (GSIS) involves interplay between metabolic and cationic events. Seminal contributions from multiple laboratories affirm essential roles for small G-proteins (Rac1, Cdc42, Arf6, Rab27A) in GSIS. Activation of these signalling proteins promotes cytoskeletal remodeling, transport and docking of insulin granules on the plasma membrane for exocytotic secretion of insulin. Evidence in rodent and human islets suggests key roles for lipidation (farnesylation and geranylgeranylation) of these G-proteins for their targeting to appropriate cellular compartments for optimal regulation of effectors leading to GSIS...
September 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28878338/the-clinical-characteristics-of-asian-patients-with-classical-type-hutchinson-gilford-progeria-syndrome
#7
Nanae Sato-Kawano, Minoru Takemoto, Emiko Okabe, Koutaro Yokote, Muneaki Matsuo, Rika Kosaki, Kenji Ihara
Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare genetic disorder that shows a characteristic progeria phenotype. We conducted a questionnaire survey of 1173 tertiary hospitals in Japan and reviewed the academic reports, to identify the characteristics of Asian patients with classical HGPS. As a result, four Japanese patients were identified; this was estimated to account for approximately two-third of the prevalence in Japan. Three Asian patients who had definitively been diagnosed with classical HGPS were identified in the literature; in total, the clinical characteristics of seven patients were evaluated...
September 7, 2017: Journal of Human Genetics
https://www.readbyqxmd.com/read/28854674/increasing-the-intracellular-isoprenoid-pool-in-saccharomyces-cerevisiae-by-structural-fine-tuning-of-a-bifunctional-farnesyl-diphosphate-synthase
#8
Sebastián Rubat, Ignacio Varas, Romina Sepúlveda, Daniel Almonacid, Fernando González-Nilo, Eduardo Agosin
Farnesyl diphosphate synthase (FPPS) is a key enzyme responsible for the supply of isoprenoid precursors for several essential metabolites, including sterols, dolichols and ubiquinone. In Saccharomyces cerevisiae, FPPS catalyzes the sequential condensation of two molecules of isopentenyl diphosphate (IPP) with dimethylallyl diphosphate (DMAPP), producing geranyl diphosphate (GPP) and farnesyl diphosphate (FPP). Critical amino acid residues that determine product chain length were determined by a comparative study of strict GPP synthases versus strict FPPS...
June 1, 2017: FEMS Yeast Research
https://www.readbyqxmd.com/read/28843826/zoledronic-acid-an-fpps-inhibitor-ameliorates-liver-steatosis-through-inhibiting-hepatic-de-novo-lipogenesis
#9
Qiaoli Tang, Shan Jiang, Wenjun Jia, Di Shen, Yudong Qiu, Yue Zhao, Bin Xue, Chaojun Li
Currently, there is no standard therapy for non-alcoholic fatty liver disease (NAFLD), and statins have been developed as a first-line pharmaceutical therapeutic option for NAFLD-associated dyslipidemia. However, prolonged statins therapy has side effects, as statins inhibit HMG-CoA reductase, an enzyme at the very beginning of the mevalonate pathway. Here, we found that zoledronic acid (ZA), an inhibitor of farnesyl diphosphate synthase in the downstream mevalonate pathway, could attenuate hepatic lipid accumulation and improve liver injury in both high-fat diet-induced C57BL/6J mice and ob/ob mice...
August 24, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28843818/perillyl-alcohol-exhibits-in-vitro-inhibitory-activity-against-plasmodium-falciparum-and-protects-against-experimental-cerebral-malaria
#10
Adriana A Marin Rodriguez, Leonardo J M Carvalho, Emilia A Kimura, Alejandro M Katzin
The development of new drugs is one of the strategies to control malaria. Isoprenoid biosynthesis in Plasmodium falciparum is an essential pathway for parasite survival, and therefore a potential target for new antimalarial drugs. Indeed, plant-derived secondary metabolites such as terpenes exhibit antimalarial activity in vitro by inhibiting isoprenoid biosynthesis in P. falciparum. In this study, the in vitro antiplasmodial activity of perillyl alcohol (POH) was evaluated, along with its in vitro toxicity and its effect on the isoprenylation process...
August 23, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28814891/diabetes-and-dyslipidemia-characterizing-lipoprotein-metabolism
#11
REVIEW
G H Tomkin, D Owens
Premature atherosclerosis in diabetes accounts for much of the decreased life span. New treatments have reduced this risk considerably. This review explores the relationship among the disturbances in glucose, lipid, and bile salt metabolic pathways that occur in diabetes. In particular, excess nutrient intake and starvation have major metabolic effects, which have allowed us new insights into the disturbance that occurs in diabetes. Metabolic regulators such as the forkhead transcription factors, the farnesyl X transcription factors, and the fibroblast growth factors have become important players in our understanding of the dysregulation of metabolism in diabetes and overnutrition...
2017: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
https://www.readbyqxmd.com/read/28813599/tetraterpene-synthase-substrate-and-product-specificity-in-the-green-microalga-botryococcus-braunii-race-l
#12
Hem R Thapa, Su Tang, James C Sacchettini, Timothy P Devarenne
Recently, the biosynthetic pathway for lycopadiene, a C40 tetraterpenoid hydrocarbon, was deciphered from the L race of Botryococcus braunii, an alga that produces hydrocarbon oils capable of being converted into combustible fuels. The lycopadiene pathway is initiated by the squalene synthase (SS)-like enzyme lycopaoctaene synthase (LOS), which catalyzes the head-to-head condensation of two C20 geranylgeranyl diphosphate (GGPP) molecules to produce C40 lycopaoctaene. LOS shows unusual substrate promiscuity for SS or SS-like enzymes by utilizing C15 farnesyl diphosphate (FPP) and C20 phytyl diphosphate in addition to GGPP as substrates...
August 25, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28809830/overexpression-and-purification-of-human-cis-prenyltransferase-in-escherichia-coli
#13
Ilan Edri, Michal Goldenberg, Michal Lisnyansky, Roi Strulovich, Hadas Newman, Anat Loewenstein, Daniel Khananshvili, Moshe Giladi, Yoni Haitin
Prenyltransferases (PT) are a group of enzymes that catalyze chain elongation of allylic diphosphate using isopentenyl diphosphate (IPP) via multiple condensation reactions. DHDDS (dehydrodolichyl diphosphate synthase) is a eukaryotic long-chain cis-PT (forming cis double bonds from the condensation reaction) that catalyzes chain elongation of farnesyl diphosphate (FPP, an allylic diphosphate) via multiple condensations with isopentenyl diphosphate (IPP). DHDDS is of biomedical importance, as a non-conservative mutation (K42E) in the enzyme results in retinitis pigmentosa, ultimately leading to blindness...
August 3, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28808351/inhibition-of-the-mevalonate-pathway-augments-the-activity-of-pitavastatin-against-ovarian-cancer-cells
#14
Marwan Ibrahim Abdullah, Mohammed Najim Abed, Alan Richardson
Only 40% of patients with advanced ovarian cancer survive more than 5 years. We have previously shown that pitavastatin induces regression of ovarian cancer xenografts in mice. To evaluate whether the response of ovarian cancer cells to pitavastatin is potentiated by farnesyl diphosphate synthase inhibitors or geranylgeraniol transferase I inhibitors, we evaluated combinations of pitavastatin with zoledronic acid, risedronate and GGTI-2133 in a panel of ovarian cancer cells. Pitavastatin (IC50 = 0.6-14 μM), zoledronic acid (IC50 = 21-57 μM), risedronate (IC50 > 100 μM) or GGTI-2133 (IC50 > 25 μM) inhibited the growth of ovarian cancer cell cultures...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28799296/traversing-biosynthetic-carbocation-landscapes-in-the-total-synthesis-of-andrastin-and-terretonin-meroterpenes
#15
Gong Xu, Masha Elkin, Dean Tantillo, Timothy Newhouse, Thomas Maimone
Meroterpenes derived from dimethylorsellinic acid (DMOA) and farnesyl pyrophosphate have attracted much biosynthetic attention, yet only recently have synthetic solutions to any family members appeared. A key point of divergence in DMOA-derived meroterpene biosynthesis is the protoaustinoid A carbocation which can be diverted to either the berkeleyone, andrastin, or terretonin structural classes via cyclase-controlled rearrangement pathways. Herein we show that the protoaustinoid bicyclo[3.3.1]nonane nucleus can be reverted to either andrastin or terretonin ring systems under abiotic reaction conditions...
August 10, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28765912/disorder-of-the-mevalonate-pathway-inhibits-calcium-induced-differentiation-of-keratinocytes
#16
Rui Jin, Xin Luo, Kang Luan, Li Liu, Liang-Dan Sun, Sen Yang, Sheng-Quan Zhang, Xue-Jun Zhang
Mutation of genes encoding the enzymes of the mevalonate pathway cause a variety of diseases, including skin disorders. Mutation of four genes in this pathway, including mevalonate kinase, phosphomevalonate kinase, mevalonate diphosphate decarboxylase and farnesyl diphosphate synthase, have demonstrated to be responsible for porokeratosis (PK). However, the pathogenesis of PK remains unclear. In the present study, specific enzyme inhibitors of the mevalonate pathway, including pravastatin (PRA), alendronate (ALD), farnesyl transferase inhibitor (FTI‑277) and geranylgeranyl transferase inhibitor (GGTI‑298), were used to investigate the effect on differentiation of keratinocytes (KCs)...
October 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28762089/secondary-metabolites-from-higher-fungi
#17
He-Ping Chen, Ji-Kai Liu
Secondary metabolites of higher fungi (mushrooms) are an underexplored resource compared to plant-derived secondary metabolites. An increasing interest in mushroom natural products has been noted in recent years. This chapter gives a comprehensive overview of the secondary metabolites from higher fungi, with 765 references highlighting the isolation, structure elucidation, biological activities, chemical syntheses, and biosynthesis of pigments, nitrogen-containing compounds, and terpenoids from mushrooms. Mushroom toxins are also included in each section...
2017: Progress in the Chemistry of Organic Natural Products
https://www.readbyqxmd.com/read/28747716/burn-induced-muscle-metabolic-derangements-and-mitochondrial-dysfunction-are-associated-with-activation-of-hif-1%C3%AE-and-mtorc1-role-of-protein-farnesylation
#18
Harumasa Nakazawa, Kazuhiro Ikeda, Shohei Shinozaki, Masayuki Kobayashi, Yuichi Ikegami, Ming Fu, Tomoyuki Nakamura, Shingo Yasuhara, Yong-Ming Yu, J A Jeevendra Martyn, Ronald G Tompkins, Kentaro Shimokado, Tomoko Yorozu, Hideki Ito, Satoshi Inoue, Masao Kaneki
Metabolic derangements are a clinically significant complication of major trauma (e.g., burn injury) and include various aspects of metabolism, such as insulin resistance, muscle wasting, mitochondrial dysfunction and hyperlactatemia. Nonetheless, the molecular pathogenesis and the relation between these diverse metabolic alterations are poorly understood. We have previously shown that burn increases farnesyltransferase (FTase) expression and protein farnesylation and that FTase inhibitor (FTI) prevents burn-induced hyperlactatemia, insulin resistance, and increased proteolysis in mouse skeletal muscle...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28741056/chlorophyll-a-with-a-farnesyl-tail-in-thermophilic-cyanobacteria
#19
Jessica M Wiwczar, Amy M LaFountain, Jimin Wang, Harry A Frank, Gary W Brudvig
Photosystem II (PSII) of oxygenic photosynthetic organisms normally contains exclusively chlorophyll a (Chl a) as its major light-harvesting pigment. Chl a canonically consists of the chlorin headgroup with a 20-carbon, 4-isoprene unit, phytyl tail. We have examined the 1.9 Å crystal structure of PSII from thermophilic cyanobacteria reported by Shen and coworkers in 2012 (PDB accession of 3ARC/3WU2). A newly refined electron density map from this structure, presented here, reveals that some assignments of the cofactors may be different from those modeled in the 3ARC/3WU2 structure, including a specific Chl a that appears to have a truncated tail by one isoprene unit...
July 24, 2017: Photosynthesis Research
https://www.readbyqxmd.com/read/28730878/investigational-drugs-in-development-for-hepatitis-d
#20
REVIEW
Mario Rizzetto
Treatment of chronic hepatitis D still relies on Interferon. To improve efficacy, new therapeutic strategies are in development which aim to deprive the Hepatitis D Virus (HDV) of functions of the Hepatitis B Virus and of the host required for its life-cycle. Areas covered: The therapeutic options are; 1) The inhibition of the farnesylation of the large HD-protein permissive of virion assembly with Lonafarnib, 2) The blocking of HBsAg entry into cells with Myrcludex B via the inhibition of the Sodium Taurocholate Cotransporting Receptor, to prevent the spreading of HDV to uninfected hepatocytes, 3) The reduction of subviral HBsAg particles by REP 2139, leading to diminished virion morphogenesis ...
September 2017: Expert Opinion on Investigational Drugs
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