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991.
Melissa Brazier-Hicks Kathryn M. Evans Markus C. Gershater Horst Puschmann Patrick G. Steel Robert Edwards 《The Journal of biological chemistry》2009,284(27):17926-17934
Flavonoids normally accumulate in plants as O-glycosylated derivatives, but several species, including major cereal crops, predominantly synthesize flavone-C-glycosides, which are stable to hydrolysis and are biologically active both in planta and as dietary components. An enzyme (OsCGT) catalyzing the UDP-glucose-dependent C-glucosylation of 2-hydroxyflavanone precursors of flavonoids has been identified and cloned from rice (Oryza sativa ssp. indica), with a similar protein characterized in wheat (Triticum aestivum L.). OsCGT is a 49-kDa family 1 glycosyltransferase related to known O-glucosyltransferases. The recombinant enzyme C-glucosylated 2-hydroxyflavanones but had negligible O-glucosyltransferase activity with flavonoid acceptors. Enzyme chemistry studies suggested that OsCGT preferentially C-glucosylated the dibenzoylmethane tautomers formed in equilibrium with 2-hydroxyflavanones. The resulting 2-hydroxyflavanone-C-glucosides were unstable and spontaneously dehydrated in vitro to yield a mixture of 6C- and 8C-glucosyl derivatives of the respective flavones. In contrast, in planta, only the respective 6C-glucosides accumulated. Consistent with this selectivity in glycosylation product, a dehydratase activity that preferentially converted 2-hydroxyflavanone-C-glucosides to the corresponding flavone-6C-glucosides was identified in both rice and wheat. Our results demonstrate that cereal crops synthesize C-glucosylated flavones through the concerted action of a CGT and dehydratase acting on activated 2-hydroxyflavanones, as an alternative means of generating flavonoid metabolites.The glycosylation of natural products with sugars through carbon–carbon bonds is a biochemically demanding reaction that gives rise to stable metabolites exhibiting the combined activity of both the secondary metabolite acceptor and sugar (1). C-Glycosides are formed in microbes, plants, and insects, where they serve a diverse range of functions including acting as siderophores, antibiotics, antioxidants, attractants, and feeding deterrents (1, 2). Despite their importance in conferring biological activity, the C-glycosyltransferases (CGTs)2 responsible for forming these glycosidic bonds have attracted relatively little attention. As a rare exception, a CGT that catalyzed the C-glucosylation of the siderophore enterobactin has been characterized in Escherichia coli (3). Similarly, an enzyme (UrdGT2) that C-conjugated a polyketide intermediate with d-olivose has also been identified as a component of the pathway leading to the biosynthesis of the antibiotic urdamycin A in Streptomyces fradiae (4, 5). Analyses of the amino acid sequences of these two CGTs place them in family 1 of the 91 glycosyltransferase families classified to date (6). Family 1 enzymes are inverting glycosyltransferases that utilize nucleotide-diphospho-sugars as activated donors to conjugate small molecule acceptors, most typically to form ether glycosidic bonds. The fact that microbial CGTs are related to enzymes that exhibit O-glycosyltransferase (OGT) activity suggests that relatively minor modifications to active site chemistry facilitate the more unusual C-conjugation. In the case of UrdGT2, CGT activity appears to be associated with the presence of a unique aspartate residue that activates the acceptor for C9 glycosylation (5). Intriguingly UrdGT2 also O-glycosylates artificial substrates (5), confirming that in microorganisms, there are no fundamental differences in the evolutionary origins of CGTs and OGTs. However, although the enzyme chemistry of OGTs has been well described, the exact mechanism by which C-glycosylation is achieved is still poorly understood (7).C-Glycosylation in plants has received little attention despite the common occurrence of such secondary metabolites in major cereal crops and medicinal species (2). The most commonly abundant C-glycosylated natural products in plants are the flavonoids, a large group of polyphenolic compounds with diverse protective and attractant functions (8). Flavonoids normally accumulate in the vacuoles of plant tissues as their respective O-linked glycosidic conjugates (Fig. 1A, compound 3). However, in at least 20 families of angiosperms, flavonoids also accumulate as the respective C-glycosides (8). As such, these derivatives are major secondary metabolites in maize, wheat, and rice (2, 8). In these cereals, C-glycosides of the simple flavones apigenin and/or luteolin predominate, with conjugation occurring singly or doubly at the C-8 and/or C-6 position (Fig. 1B). Activities ascribed to these plant secondary metabolites include them functioning as antioxidants (9, 10), insect feeding attractants (11), antimicrobial agents (12), promoters of mycorrhizal symbioses (13), and UV-protective pigments (14). From a dietary perspective, these compounds have also been ascribed both positive and negative biological activities. Thus, in vitro, flavone-C-glycosides can counteract tissue oxidation (15), inflammation, and cancer development (16). However, millet diets containing high levels of C-glucosylflavones have been shown to suppress thyroid iodine uptake in rats and have the potential to cause goitrogenic effects (17).Open in a separate windowFIGURE 1.Glycosylflavone biosynthesis in plants. A, FNS converts flavanones (compound 1) to flavones (compound 2), which are then conjugated by an OGT. B, in cereals, the flavanone also undergoes conversion to the 2-hydroxyflavanone (compound 4a), which exists in equilibrium with its open-chain form (compound 4b), the latter apparently being acted on by the C-glucosyltransferase (CGT) to produce 2-hydroxyflavanone C-glucosides (compound 5, a–c). These are then dehydrated to yield the flavone-6C-glucoside (compound 6) and flavone-8C-glucoside (compound 7). C and D, the hydroxylation (C) and C-glycosylation (D) of the flavonoids referred to under “Results.”Relatively little is known about flavone-C-glycoside biogenesis. The flavanones, which are core intermediates of the flavonoid pathway, are the most likely precursors (Fig. 1A, compound 1). Studies in buckwheat (Fagopyrum esculentum) demonstrated that 2-hydroxyflavanones (Fig. 1B, compound 4, a and b) underwent enzyme-catalyzed C-glucosylation and were the direct precursors of flavone-C-glycosides (18, 19). However, the identity of the respective CGTs has not been determined, and the biochemistry underlying this unusual conjugation remains unresolved. With an interest in the natural products chemistry and the biotechnological applications of this important branch of plant secondary metabolism, we now report on the purification, identification, and characterization of CGTs responsible for flavone-C-glycoside synthesis in rice (Oryza sativa ssp. indica) and wheat (Triticum aestivum L.). 相似文献
992.
Kamyar Hadian Michelle Vincendeau Nina M?usbacher Daniel Nagel Stefanie M. Hauck Marius Ueffing Abraham Loyter Thomas Werner Horst Wolff Ruth Brack-Werner 《The Journal of biological chemistry》2009,284(48):33384-33391
The Rev protein is a key regulator of human immunodeficiency virus type 1 (HIV-1) gene expression. Rev is primarily known as an adaptor protein for nuclear export of HIV RNAs. However, Rev also contributes to numerous other processes by less well known mechanisms. Understanding the functional nature of Rev requires extensive knowledge of its cellular interaction partners. Here we demonstrate that Rev interacts with members of a large family of multifunctional host cell factors called hnRNPs. Rev employs amino acids 9–14 for specific binding to the heterogeneous nuclear ribonucleoproteins (hnRNP) A1, Q, K, R, and U. In addition, Rev interacts with hnRNP E1 and E2 by a different mechanism. The set of hnRNPs recognized by the N terminus of Rev feature RGG boxes. Exemplary testing of hnRNP A1 revealed a critical role of arginine residues within the RGG box for interaction with Rev. Finally, we demonstrate that expression levels of hnRNP A1, Q, K, R, and U influence HIV-1 production by persistently infected astrocytes, linking these hnRNPs to HIV replication. The novel interaction of HIV-1 Rev with functionally diverse hnRNPs lends further support to the idea that Rev is a multifunctional protein and may be involved in coupling HIV replication to diverse cellular processes and promoting virus-host cell interactions. 相似文献
993.
Martin Spichty Antoine Taly Franz Hagn Horst Kessler Sofia Barluenga Nicolas Winssinger Martin Karplus 《Biophysical chemistry》2009
We determine the binding mode of a macrocyclic radicicol-like oxime to yeast HSP90 by combining computer simulations and experimental measurements. We sample the macrocyclic scaffold of the unbound ligand by parallel tempering simulations and dock the most populated conformations to yeast HSP90. Docking poses are then evaluated by the use of binding free energy estimations with the linear interaction energy method. Comparison of QM/MM-calculated NMR chemical shifts with experimental shift data for a selective subset of backbone 15N provides an additional evaluation criteria. As a final test we check the binding modes against available structure–activity-relationships. We find that the most likely binding mode of the oxime to yeast HSP90 is very similar to the known structure of the radicicol–HSP90 complex. 相似文献
994.
995.
Most terrestrial plants live in symbiosis with arbuscular mycorrhizal (AM) fungi. Studies on the direct interaction between
plants and mycorrhizal fungi are numerous whereas studies on the indirect interaction between such fungi and herbivores feeding
on aboveground plant parts are scarce. We studied the impact of AM symbiosis on host plant choice and life history of an acarine
surface piercing-sucking herbivore, the polyphagous two-spotted spider mite Tetranychus urticae. Experiments were performed on detached leaflets taken from common bean plants (Phaseolus vulgaris) colonized or not colonized by the AM fungus Glomus mosseae. T. urticae females were subjected to choice tests between leaves from mycorrhizal and non-mycorrhizal plants. Juvenile survival and
development, adult female survival, oviposition rate and offspring sex ratio were measured in order to estimate the population
growth parameters of T. urticae on either substrate. Moreover, we analyzed the macro- and micronutrient concentration of the aboveground plant parts. Adult
T. urticae females preferentially resided and oviposited on mycorrhizal versus non-mycorrhizal leaflets. AM symbiosis significantly
decreased embryonic development time and increased the overall oviposition rate as well as the proportion of female offspring
produced during peak oviposition. Altogether, the improved life history parameters resulted in significant changes in net
reproductive rate, intrinsic rate of increase, doubling time and finite rate of increase. Aboveground parts of colonized plants
showed higher concentrations of P and K whereas Mn and Zn were both found at lower levels. This is the first study documenting
the effect of AM symbiosis on the population growth rates of a herbivore, tracking the changes in life history characteristics
throughout the life cycle. We discuss the AM-plant-herbivore interaction in relation to plant quality, herbivore feeding type
and site and the evolutionary implications in a multi-trophic context. 相似文献
996.
997.
Malika Chegary Heleen te Brinke Jos P.N. Ruiter Frits A. Wijburg Maria S.K. Stoll Paul E. Minkler Michel van Weeghel Horst Schulz Charles L. Hoppel Ronald J.A. Wanders Sander M. Houten 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2009,1791(8):806-815
Several mouse models for mitochondrial fatty acid β-oxidation (FAO) defects have been developed. So far, these models have contributed little to our current understanding of the pathophysiology. The objective of this study was to explore differences between murine and human FAO. Using a combination of analytical, biochemical and molecular methods, we compared fibroblasts of long chain acyl-CoA dehydrogenase knockout (LCAD−/−), very long chain acyl-CoA dehydrogenase knockout (VLCAD−/−) and wild type mice with fibroblasts of VLCAD-deficient patients and human controls. We show that in mice, LCAD and VLCAD have overlapping and distinct roles in FAO. The absence of VLCAD is apparently fully compensated, whereas LCAD deficiency is not. LCAD plays an essential role in the oxidation of unsaturated fatty acids such as oleic acid, but seems redundant in the oxidation of saturated fatty acids. In strong contrast, LCAD is neither detectable at the mRNA level nor at the protein level in men, making VLCAD indispensable in FAO. Our findings open new avenues to employ the existing mouse models to study the pathophysiology of human FAO defects. 相似文献
998.
Tobias Tenenbaum Thalia Papandreou Dorothee Gellrich Ulrike Friedrichs Annette Seibt Rüdiger Adam Corinna Wewer Hans-Joachim Galla Christian Schwerk Horst Schroten 《Cellular microbiology》2009,11(2):323-336
Previous experimental studies in a standard Transwell culture system have shown Streptococcus suis ability to compromise barrier function of porcine choroid plexus epithelial cells (PCPEC). The development of an 'inverted' Transwell filter system of PCPEC enables us now for the first time to investigate bacterial invasion and translocation from the physiologically relevant basolateral (blood) to the apical (cerobrospinal fluid) side. Most importantly, we observed specific invasion and translocation of S. suis across the PCPEC exclusively from the basolateral side. During this process, bacterial viability and the presence of a capsule as well as cytoskeletal regulation of PCPEC seemed to play an important role. No loss of barrier function was observed. Bacterial translocation could be significantly inhibited by the phosphatidylinositol 3-kinase inhibitor LY294002, but not by its inactive analogue Ly303511 or dexamethasone. Apotome imaging as well as electron microscopy revealed intracellular bacteria often in cell vacuoles. Thus, possibly regulated by the presence of a capsule, S. suis induces signals that depend on the lipid kinase phosphatidylinositol 3-kinase pathway, which paves the way for cellular uptake during the bacterial transcellular translocation process. Taken together, our data underline the relevance of the blood–cerebrospinal fluid barrier as a gate for bacterial entry into the central nervous system. 相似文献
999.
Heike Mikschofsky Martin Hammer Jörg Schmidtke Patricia König Günther Keil Horst Schirrmeier Kerstin Schmidt Inge Broer 《In vitro cellular & developmental biology. Plant》2009,45(6):740-749
Carrot suspension cultures are efficient production systems for plant-made pharmaceuticals (PMP); however, frequently, the
reduction of transgene expression in long-running transgenic cell lines limits the productivity. Freshly induced carrot suspensions
have been identified for a constant and high biomass production with optimization of culture conditions and cultivars. A small-volume
monitoring method was adapted to freshly induced carrot suspension that minimized the heterogeneity of freshly induced meristematic
carrot cell lines. Using this system combined with the adaptation of growth conditions, we identified the cultivar Rote Riesen
as having the highest increase in dry biomass with an average of 6.5 g/L weekly, stable and consistent after 8 wk. As a model
PMP, VP60—the capsid protein from the rabbit hemorrhagic disease virus—was produced in a carrot suspension with a maximal
accumulation of 2.4 μg/g dry mass. The developed method guarantees comparable investigations of different transgene expression
in various freshly induced small-volume carrot cell lines. 相似文献
1000.
Claus Kemkemer Matthias Kohn David N Cooper Lutz Froenicke Josef Högel Horst Hameister Hildegard Kehrer-Sawatzki 《BMC evolutionary biology》2009,9(1):84-24