Bibliografie tematiche / Prenol kinases

Letteratura scientifica selezionata sul tema "Prenol kinases"

Autore: Grafiati

Pubblicato: 25 maggio 2024

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Articoli di riviste sul tema "Prenol kinases":

Crispim, Marcell, Ignasi Bofill Verdaguer, Agustín Hernández, Thales Kronenberger, Àngel Fenollar, Lydia Fumiko Yamaguchi, María Pía Alberione et al. "Beyond the MEP Pathway: A novel kinase required for prenol utilization by malaria parasites". PLOS Pathogens 20, n. 1 (26 gennaio 2024): e1011557. http://dx.doi.org/10.1371/journal.ppat.1011557.

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A proposed treatment for malaria is a combination of fosmidomycin and clindamycin. Both compounds inhibit the methylerythritol 4-phosphate (MEP) pathway, the parasitic source of farnesyl and geranylgeranyl pyrophosphate (FPP and GGPP, respectively). Both FPP and GGPP are crucial for the biosynthesis of several essential metabolites such as ubiquinone and dolichol, as well as for protein prenylation. Dietary prenols, such as farnesol (FOH) and geranylgeraniol (GGOH), can rescue parasites from MEP inhibitors, suggesting the existence of a missing pathway for prenol salvage via phosphorylation. In this study, we identified a gene in the genome of P. falciparum, encoding a transmembrane prenol kinase (PolK) involved in the salvage of FOH and GGOH. The enzyme was expressed in Saccharomyces cerevisiae, and its FOH/GGOH kinase activities were experimentally validated. Furthermore, conditional knockout parasites (Δ-PolK) were created to investigate the biological importance of the FOH/GGOH salvage pathway. Δ-PolK parasites were viable but displayed increased susceptibility to fosmidomycin. Their sensitivity to MEP inhibitors could not be rescued by adding prenols. Additionally, Δ-PolK parasites lost their capability to utilize prenols for protein prenylation. Experiments using culture medium supplemented with whole/delipidated human plasma in transgenic parasites revealed that human plasma has components that can diminish the effectiveness of fosmidomycin. Mass spectrometry tests indicated that both bovine supplements used in culture and human plasma contain GGOH. These findings suggest that the FOH/GGOH salvage pathway might offer an alternate source of isoprenoids for malaria parasites when de novo biosynthesis is inhibited. This study also identifies a novel kind of enzyme related to isoprenoid metabolism.

Lee, Miriam, William Wickner e Hongki Song. "A Rab prenyl membrane-anchor allows effector recognition to be regulated by guanine nucleotide". Proceedings of the National Academy of Sciences 117, n. 14 (25 marzo 2020): 7739–44. http://dx.doi.org/10.1073/pnas.2000923117.

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Membrane fusion is catalyzed by conserved proteins R, Qa, Qb, and Qc SNAREs, which form tetrameric RQaQbQc complexes between membranes; SNARE chaperones of the SM, Sec17/αSNAP, and Sec18/NSF families; Rab-GTPases (Rabs); and Rab effectors. Rabs are anchored to membranes by C-terminal prenyl groups, but can also function when anchored by an apolar polypeptide. Rabs are regulated by GTPase-activating proteins (GAPs), activating the hydrolysis of bound GTP. We have reconstituted fusion with pure components from yeast vacuoles including SNAREs, the HOPS (homotypic fusion and vacuole protein sorting) tethering and SNARE-assembly complex, and the Rab Ypt7, bound to membranes by either C-terminal prenyl groups (Ypt7-pr) or a recombinant transmembrane anchor (Ypt7-tm). We now report that HOPS-dependent fusion occurs with Ypt7 anchored by either means, but only Ypt7-pr requires GTP for activation and is inactive either with bound GDP or without bound guanine nucleotide. In contrast, Ypt7-tm is constitutively active for HOPS-dependent fusion, independent of bound guanine nucleotide. Fusion inhibition by the GAP Gyp1-46 is not limited to Ypt7-tm with bound GTP, indicating that this GAP has an additional mode of regulating fusion. Phosphorylation of HOPS by the vacuolar kinase Yck3 renders fusion strictly dependent on GTP-activated Ypt7, whether bound to membranes by prenyl or transmembrane anchor. The binding of GTP or GDP constitutes a selective switch for Ypt7, but with Ypt7-tm, this switch is only read by HOPS after phosphorylation to P-HOPS by its physiological kinase Yck3. The prenyl anchor of Ypt7 allows both HOPS and P-HOPS to be regulated by Ypt7-bound guanine nucleotide.

Qiu, Cong, Yang Liu, Yangbao Wu, Linguo Zhao e Jianjun Pei. "Functional Characterization and Screening of Promiscuous Kinases and Isopentenyl Phosphate Kinases for the Synthesis of DMAPP via a One-Pot Enzymatic Cascade". International Journal of Molecular Sciences 23, n. 21 (26 ottobre 2022): 12904. http://dx.doi.org/10.3390/ijms232112904.

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Dimethylallyl diphosphate (DMAPP) is a key intermediate metabolite in the synthesis of isoprenoids and is also the prenyl donor for biosynthesizing prenylated flavonoids. However, it is difficult to prepare DMAPP via chemical and enzymatic methods. In this study, three promiscuous kinases from Shigella flexneri (SfPK), Escherichia coli (EcPK), and Saccharomyces cerevisiae (ScPK) and three isopentenyl phosphate kinases from Methanolobus tindarius (MtIPK), Methanothermobacter thermautotrophicus str. Delta H (MthIPK), and Arabidopsis thaliana (AtIPK) were cloned and expressed in Escherichia coli. The enzymatic properties of recombinant enzymes were determined. The Kcat/Km value of SfPK for DMA was 6875 s−1 M−1, which was significantly higher than those of EcPK and ScPK. The Kcat/Km value of MtIPK for DMAP was 402.9 s−1 M−1, which was ~400% of that of MthIPK. SfPK was stable at pH 7.0–9.5 and had a 1 h half-life at 65 °C. MtIPK was stable at pH 6.0–8.5 and had a 1 h half-life at 50 °C. The stability of SfPK and MtIPK was better than that of the other enzymes. Thus, SfPK and MtIPK were chosen to develop a one-pot enzymatic cascade for producing DMAPP from DMA because of their catalytic efficiency and stability. The optimal ratio between SfPK and MtIPK was 1:8. The optimal pH and temperature for the one-pot enzymatic cascade were 7.0 and 35 °C, respectively. The optimal concentrations of ATP and DMA were 10 and 80 mM, respectively. Finally, maximum DMAPP production reached 1.23 mM at 1 h under optimal conditions. Therefore, the enzymatic method described herein for the biosynthesis of DMAPP from DMA can be widely used for the synthesis of isoprenoids and prenylated flavonoids.

Lundquist, Peter K., Anton Poliakov, Lisa Giacomelli, Giulia Friso, Mason Appel, Ryan P. McQuinn, Stuart B. Krasnoff et al. "Loss of Plastoglobule Kinases ABC1K1 and ABC1K3 Causes Conditional Degreening, Modified Prenyl-Lipids, and Recruitment of the Jasmonic Acid Pathway". Plant Cell 25, n. 5 (maggio 2013): 1818–39. http://dx.doi.org/10.1105/tpc.113.111120.

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Grant, Benjamin M. M., Masahiro Enomoto, Sung-In Back, Ki-Young Lee, Teklab Gebregiworgis, Noboru Ishiyama, Mitsuhiko Ikura e Christopher B. Marshall. "Calmodulin disrupts plasma membrane localization of farnesylated KRAS4b by sequestering its lipid moiety". Science Signaling 13, n. 625 (31 marzo 2020): eaaz0344. http://dx.doi.org/10.1126/scisignal.aaz0344.

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KRAS4b is a small guanosine triphosphatase (GTPase) protein that regulates several signal transduction pathways that underlie cell proliferation, differentiation, and survival. KRAS4b function requires prenylation of its C terminus and recruitment to the plasma membrane, where KRAS4b activates effector proteins including the RAF family of kinases. The Ca2+-sensing protein calmodulin (CaM) has been suggested to regulate the localization of KRAS4b through direct, Ca2+-dependent interaction, but how CaM and KRAS4b functionally interact is controversial. Here, we determined a crystal structure, which was supported by solution nuclear magnetic resonance (NMR), that revealed the sequestration of the prenyl moiety of KRAS4b in the hydrophobic pocket of the C-terminal lobe of Ca2+-bound CaM. Our engineered fluorescence resonance energy transfer (FRET)–based biosensor probes (CaMeRAS) showed that, upon stimulation of Ca2+ influx by extracellular ligands, KRAS4b reversibly translocated in a Ca2+-CaM–dependent manner from the plasma membrane to the cytoplasm in live HeLa and HEK293 cells. These results reveal a mechanism underlying the inhibition of KRAS4b activity by Ca2+ signaling pathways.

Wang, Yi-Xuan, Yi-Yuan Jin, Jie Wang, Zi-Cheng Zhao, Ke-Wen Xue, He Xiong, Hui-Lian Che, Yun-Jun Ge e Guo-Sheng Wu. "Icaritin Derivative IC2 Induces Cytoprotective Autophagy of Breast Cancer Cells via SCD1 Inhibition". Molecules 28, n. 3 (22 gennaio 2023): 1109. http://dx.doi.org/10.3390/molecules28031109.

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Breast cancer is one of the most prevalent malignancies and the leading cause of cancer-associated mortality in China. Icaritin (ICT), a prenyl flavonoid derived from the Epimedium Genus, has been proven to inhibit the proliferation and stemness of breast cancer cells. Our previous study demonstrated that IC2, a derivative of ICT, could induce breast cancer cell apoptosis by Stearoyl-CoA desaturase 1 (SCD1) inhibition. The present study further investigated the mechanism of the inhibitory effects of IC2 on breast cancer cells in vitro and in vivo. Our results proved that IC2 could stimulate autophagy in breast cancer cells with the activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling and mitogen-activated protein kinase (MAPK) signaling. Combination treatment of the AMPK inhibitor decreased IC2-induced autophagy while it markedly enhanced IC2-induced apoptosis. In common with IC2-induced apoptosis, SCD1 overexpression or the addition of exogenous oleic acid (OA) could also alleviate IC2-induced autophagy. In vivo assays additionally demonstrated that IC2 treatment markedly inhibited tumor growth in a mouse breast cancer xenograft model. Overall, our study was the first to demonstrate that IC2 induced cytoprotective autophagy by SCD1 inhibition in breast cancer cells and that the autophagy inhibitor markedly enhanced the anticancer activity of IC2. Therefore, IC2 was a potential candidate compound in combination therapy for breast cancer.

Kollar, Peter, Tomáš Bárta, Stanislava Keltošová, Pavlína Trnová, Veronika Müller Závalová, Karel Šmejkal, Jan Hošek, Radek Fedr, Karel Souček e Aleš Hampl. "Flavonoid 4′-O-Methylkuwanon E fromMorus albaInduces the Differentiation of THP-1 Human Leukemia Cells". Evidence-Based Complementary and Alternative Medicine 2015 (2015): 1–8. http://dx.doi.org/10.1155/2015/251895.

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Aims. In this work we studied cytodifferentiation effects of newly characterized prenyl flavonoid 4′-O-methylkuwanon E (4ME) isolated from white mulberry (Morus albaL.).Main Methods. Cell growth and viability were measured by dye exclusion assay; cell cycle and surface antigen CD11b were monitored by flow cytometry. For the cytodifferentiation of cells the NBT reduction assay was employed. Regulatory proteins were assessed by western blotting.Key Findings. 4ME induced dose-dependent growth inhibition of THP-1 cells, which was not accompanied by toxic effect. Inhibition of cells proliferation caused by 4ME was associated with the accumulation in G1 phase and with downregulation of hyperphosphorylated pRb. Treatment with 4ME led to significant induction of NBT-reducing activity of PMA stimulated THP-1 cells and upregulation expression of differentiation-associated surface antigen CD11b. Our results suggest that monocytic differentiation induced by 4ME is connected with up-regulation of p38 kinase activity.Significance. Our study provides the first evidence that 4ME induces the differentiation of THP-1 human monocytic leukemia cells and thus is a potential cytodifferentiating anticancer agent.

Zita, Wayne, Ségolène Bressoud, Gaetan Glauser, Felix Kessler e Venkatasalam Shanmugabalaji. "Chromoplast plastoglobules recruit the carotenoid biosynthetic pathway and contribute to carotenoid accumulation during tomato fruit maturation". PLOS ONE 17, n. 12 (6 dicembre 2022): e0277774. http://dx.doi.org/10.1371/journal.pone.0277774.

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Tomato (Solanum lycopersicum) fruit maturation is associated with a developmental transition from chloroplasts (in mature green fruit) to chromoplasts (in red fruit). The hallmark red color of ripe tomatoes is due to carotenogenesis and accumulation of the red carotenoid lycopene inside chromoplasts. Plastoglobules (PG) are lipid droplets in plastids that are involved in diverse lipid metabolic pathways. In tomato, information on the possible role of PG in carotogenesis and the PG proteome is largely lacking. Here, we outline the role of PG in carotenogenesis giving particular attention to tomato fruit PG proteomes and metabolomes. The proteome analysis revealed the presence of PG-typical FBNs, ABC1K-like kinases, and metabolic enzymes, and those were decreased in the PG of tomato chromoplasts compared to chloroplasts. Notably, the complete β-carotene biosynthesis pathway was recruited to chromoplast PG, and the enzymes PHYTOENE SYNTHASE 1 (PSY-1), PHYTOENE DESATURASE (PDS), ZETA-CAROTENE DESATURASE (ZDS), and CAROTENOID ISOMERASE (CRTISO) were enriched up to twelvefold compared to chloroplast PG. We profiled the carotenoid and prenyl lipid changes in PG during the chloroplast to chromoplast transition and demonstrated large increases of lycopene and β-carotene in chromoplast PG. The PG proteome and metabolome are subject to extensive remodeling resulting in high accumulation of lycopene during the chloroplast-to-chromoplast transition. Overall, the results indicate that PGs contribute to carotenoid accumulation during tomato fruit maturation and suggest that they do so by functioning as a biosynthetic platform for carotenogenesis.

Rocha, Sonia, Daniela Ribeiro, Eduarda Fernandes e Marisa Freitas. "A Systematic Review on Anti-diabetic Properties of Chalcones". Current Medicinal Chemistry 27, n. 14 (29 aprile 2020): 2257–321. http://dx.doi.org/10.2174/0929867325666181001112226.

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: The use of anti-diabetic drugs has been increasing worldwide and the evolution of therapeutics has been enormous. Still, the currently available anti-diabetic drugs do not present the desired efficacy and are generally associated with serious adverse effects. Thus, entirely new interventions, addressing the underlying etiopathogenesis of type 2 diabetes mellitus, are required. Chalcones, secondary metabolites of terrestrial plants and precursors of the flavonoids biosynthesis, have been used for a long time in traditional medicine due to their wide-range of biological activities, from which the anti-diabetic activity stands out. : This review systematizes the information found in literature about the anti-diabetic properties of chalcones, in vitro and in vivo. Chalcones are able to exert these properties by acting in different therapeutic targets: Dipeptidyl Peptidase 4 (DPP-4); Glucose Transporter Type 4 (GLUT4), Sodium Glucose Cotransporter 2 (SGLT2), α-amylase, α-glucosidase, Aldose Reductase (ALR), Protein Tyrosine Phosphatase 1B (PTP1B), Peroxisome Proliferator-activated Receptor-gamma (PPARγ) and Adenosine Monophosphate (AMP)-activated Protein Kinase (AMPK). Chalcones are, undoubtedly, promising anti-diabetic agents, and some crucial structural features have already been established. From the Structure-Activity Relationships analysis, it can generally be stated that the presence of hydroxyl, prenyl and geranyl groups in their skeleton improves their activity for the evaluated anti-diabetic targets.

Zayoud, Morad, Einva Vax, Galit Elad Sfadia, Yoel Kloog e Itamar Goldstein. "Farnesylthiosalicylic acid reduces disease severity in the collagen type-II induced arthritis mouse model by inhibiting Ras Signaling in pathogenic T cells". Journal of Immunology 198, n. 1_Supplement (1 maggio 2017): 224.7. http://dx.doi.org/10.4049/jimmunol.198.supp.224.7.

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Abstract Background Ras proteins are vital for normal T cell activation, and downstream effectors of Ras include the MEK/ERK, PI3-kinase/AKT, and NF-kB pathways. T cells from Rheumatoid Arthritis patients exhibit abnormal activation of the Ras/MEK/ERK pathway. The small molecule Farnesylthiosalicylic acid (FTS) blocks the interaction between Ras proteins and their prenyl binding chaperones, attenuating plasma membrane localization and signaling. Objectives To investigate the immunomodulatory effect of FTS alone or combined with methotrexate (MTX) in the DBA/1 mouse collagen type-II induced arthritis (CIA) model. Methods Arthritis was induced in 8–10 week old male DBA/1 mice by immunization with collagen type-II (CII) and complete Freund’s adjuvant (CFA). Animals were treated semi-prophylactically with once daily oral FTS (100 mg/kg); weekly i.p injection of MTX (0.5 mg/kg), FTS combined with MTX, or daily oral vehicle solution (control). Arthritis severity was scored daily from disease onset until study termination and multiple immunological biomarkers of inflammation were analyzed. Results Our data from the mouse CIA model show that the therapeutic efficacy of FTS was similar to MTX, and both drugs significantly reduced arthritis severity compared to CMC controls. Importantly, FTS significantly inhibited the production of pathogenic anti-CII autoantibodies and upregulation of serum IL-6 and IL-17A compared to control arthritic mice. The in depth, multiplex, analysis of the effect of FTS on the T cell cytokine response to CII, revealed strong suppression of IL-22, IL-17, IL-9, GM-CSF and TNF production. Importantly, FTS therapy positively correlated with reduced p-ERK1/2 and p-AKT levels in splenic lymphocytes.

Più fonti

Tesi sul tema "Prenol kinases":

Couillaud, Julie. "The terpene mini-path : nouvel accès aux terpènes et exploration de l'espace chimique par une cascade enzymatique originale". Electronic Thesis or Diss., Aix-Marseille, 2021. http://www.theses.fr/2021AIXM0188.

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À ce jour, les terpénoïdes constituent la classe de produits naturels la plus abondante et diversifiée avec plus de 80000 composés décrits et dont les propriétés structurales, biologiques (antibiotique, anticancéreux, antipaludique…) et physico-chimiques (arôme, parfum, colorant…) retiennent l’attention de la communauté scientifique. Cependant, leur accès est limité par une faible disponibilité par extraction à partir de sources naturelles ; une synthèse chimique souvent coûteuse et laborieuse; et des voies de biosynthèses longues. En combinant des approches bioinformatiques, statistiques, biochimiques et de biologie moléculaire, nous avons développé la « mini-voie des terpènes », à seulement deux étapes enzymatiques, comme alternative synthétique et biosourçable pour l’accès aux DMAPP et IPP, précurseurs universels des terpènes. Cette nouvelle voie artificielle a permis la synthèse de différents terpénoïdes naturels et également non-naturels tels que des dérivés cyclobutyliques, en l’absence d’ingénierie métabolique et enzymatique. Ainsi, la mini-voie offre un accès facilité à l’ensemble des terpénoïdes et constitue un nouvel outil biosynthétique attractif pour l’exploration de la diversité de l’espace chimique des terpènes
To date, terpenoids form the most abundant and diversified class of natural products with more than 80,000 compounds whose structural, biological (antibiotic, anticancer, antimalarial, etc.) and physicochemical (flavor, fragrance, dye, etc.) properties hold the attention of the scientific community. However, their access is limited because of the low available quantity by extraction from natural sources; an often expensive and laborious chemical synthesis; and long biosynthetic pathways. By combining bioinformatic, statistical, biochemical and molecular biology approaches, we have developed the « Terpene mini-path », with only two enzymatic steps, as a synthetic and potentially bio-sourced alternative to access DMAPP and IPP, universal precursors of terpenes. This new artificial pathway allowed the synthesis of various natural and unnatural terpenoids, such as cyclobutylic derivatives, in the absence of any metabolic and enzymatic engineering. The mini-path provides thus an easy access to all terpenoids and represents an attractive new biosynthetic tool to explore the diversity of the terpene chemical space

Dominguez-Escrig, J. L. "Tyrosine kinase and prenyl transferase inhibitors as potential therapeutics in urothelial carcinoma". Thesis, University of Newcastle upon Tyne, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.427275.

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Neuser, Julia [Verfasser], Markus [Gutachter] Lange, Kai [Gutachter] Schuh e Martina [Gutachter] Prelog. "Die Rolle der Pim-1 Kinase im Zweiten Fenster der Anästhetika-induzierten Präkonditionierung / Julia Neuser ; Gutachter: Markus Lange, Kai Schuh, Martina Prelog". Würzburg : Universität Würzburg, 2020. http://d-nb.info/1219430137/34.

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