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61.
62.
Zheng Zhang Sriram Jakkaraju Joy Blain Kenneth Gogol Lei Zhao Robert C. Hartley Courtney A. Karlsson Bart L. Staker Thomas E. Edwards Lance J. Stewart Peter J. Myler Michael Clare Darren W. Begley James R. Horn Timothy J. Hagen 《Bioorganic & medicinal chemistry letters》2013,23(24):6860-6863
Published biological data suggest that the methyl erythritol phosphate (MEP) pathway, a non-mevalonate isoprenoid biosynthetic pathway, is essential for certain bacteria and other infectious disease organisms. One highly conserved enzyme in the MEP pathway is 2C-methyl-d-erythritol 2,4-cyclodiphosphate synthase (IspF). Fragment-bound complexes of IspF from Burkholderia pseudomallei were used to design and synthesize a series of molecules linking the cytidine moiety to different zinc pocket fragment binders. Testing by surface plasmon resonance (SPR) found one molecule in the series to possess binding affinity equal to that of cytidine diphosphate, despite lacking any metal-coordinating phosphate groups. Close inspection of the SPR data suggest different binding stoichiometries between IspF and test compounds. Crystallographic analysis shows important variations between the binding mode of one synthesized compound and the pose of the bound fragment from which it was designed. The binding modes of these molecules add to our structural knowledge base for IspF and suggest future refinements in this compound series. 相似文献
63.
The fine structure of the symbiotic alga isolated from the formainiferan Archaias angulatus (Fichtel et Moll) DeMontfort is typical of the Chlorophyceae of the volvocalean and chlorococcalean lines. Spherical non-motile cells, 10–14 μm in diameter, characterise the dominant life cycle phase. Long oval motile forms with truncated apices are present 3–5 days after transfer to fresh medium. The pyrenoids are embedded anteriorly in the singly bilobed chloroplast and are surrounded by a sheath of starch platelets. In spite of the non-motile state of cells in older cultures (which is perhaps a reflection of its normally symbiotic condition), the alga is identified as a species of the volvocalean genus Chlamydomonas and is named C. hedleyi sp. nov. The symbiont has no vitamin or organic requirements but growth is increased threefold in the presence of thiamine, and twofold in the presence of 1 μm glutamic acid, histidine and methionine. Urea was the best nitrogen source tested. Purines and pyrimidines did not serve as nitrogen sources. Chlamydomonas hedleyi grows well in a salinity range of 6->52‰. and a pH range of 6–8·5, 7·04 × 10-7 m carbon h-1 g-1 was fixed by the symbiont, 57% being released into the medium as a chromatographically homogeneous organic molecule provisionally identified as mannitol. 相似文献
64.
Maja Martic Ida Noémi Jakab-Simon Lærke Tvedebrink Haahr Wilfred Raymond Hagen Hans Erik Mølager Christensen 《Journal of biological inorganic chemistry》2013,18(2):261-276
Heterometallic [AgFe3S4] iron–sulfur clusters assembled in wild-type Pyrococcus furiosus ferredoxin and two variants, D14C and D14H, are characterized. The crystal structure of the [AgFe3S4] D14C variant shows that the silver(I) ion is indeed part of the cluster and is coordinated to the thiolate group of residue 14. Cyclic voltammetry shows one redox pair with a reduction potential of +220 mV versus the standard hydrogen electrode which is assigned to the [AgFe3S4]2+/+ couple. The oxidized form of the [AgFe3S4] D14C variant is stable in the presence of dioxygen, whereas the oxidized forms of the [AgFe3S4] wild type and D14H variants convert to the [Fe3S4] ferredoxin form. The monovalent d 10 silver(I) ion stabilizes the [Fe3S4]+/0 cluster fragment, as opposed to divalent d 10 metal ions, resulting in more than 0.4 V difference in reduction potentials between the silver(I) and, e.g., zinc(II) heterometallic [MFe3S4] ferredoxins. The trend in reduction potentials for the variants containing the [AgFe3S4] cluster is wild type ≤ D14C < D14H and shows the same trend as reported for the variants containing the [Fe3S4] cluster, but is different from the D14C < D14H < wild type trend reported for the [Fe4S4] ferredoxin. The similarity in the reduction potential trend for the variants containing the heterometallic [AgFe3S4] cluster and the [Fe3S4] cluster can be rationalized in terms of the electrostatic influence of the residue 14 side chains, rather than the dissociation constant of this residue, as is the case for [Fe4S4] ferredoxins. The trends in reduction potentials are in line with there being no electronic coupling between the silver(I) ion and the Fe3S4 fragment. 相似文献
65.
Ingerid J. Hagen Anna M. Billing Bernt Rønning Sindre A. Pedersen Henrik Pärn Jon Slate Henrik Jensen 《Molecular ecology resources》2013,13(3):429-439
With the advent of next generation sequencing, new avenues have opened to study genomics in wild populations of non‐model species. Here, we describe a successful approach to a genome‐wide medium density Single Nucleotide Polymorphism (SNP) panel in a non‐model species, the house sparrow (Passer domesticus), through the development of a 10 K Illumina iSelect HD BeadChip. Genomic DNA and cDNA derived from six individuals were sequenced on a 454 GS FLX system and generated a total of 1.2 million sequences, in which SNPs were detected. As no reference genome exists for the house sparrow, we used the zebra finch (Taeniopygia guttata) reference genome to determine the most likely position of each SNP. The 10 000 SNPs on the SNP‐chip were selected to be distributed evenly across 31 chromosomes, giving on average one SNP per 100 000 bp. The SNP‐chip was screened across 1968 individual house sparrows from four island populations. Of the original 10 000 SNPs, 7413 were found to be variable, and 99% of these SNPs were successfully called in at least 93% of all individuals. We used the SNP‐chip to demonstrate the ability of such genome‐wide marker data to detect population sub‐division, and compared these results to similar analyses using microsatellites. The SNP‐chip will be used to map Quantitative Trait Loci (QTL) for fitness‐related phenotypic traits in natural populations. 相似文献
66.
Patrick Stelmach Christian Wedemeyer Lena Fuest Gina Kurscheid Thorsten Gehrke Stefanie Klenke Marcus J?ger Max D. Kauther Hagen S. Bachmann 《PloS one》2016,11(2)
Aseptic loosening is a major cause of revision surgery of total hip arthroplasty (THA). Only few host factors affecting aseptic loosening have been identified until now, although they are urgently needed to identify and possibly treat those patients at higher risk for aseptic loosening. To determine whether the functional single nucleotide polymorphism (SNP) c.-938C>A (rs2279115), located in the promoter region of the BCL2 gene has an impact on aseptic loosening of THA we genotyped and analyzed 234 patients suffering from aseptic loosening and 231 patients after primary THA. The polymorphism is associated with risk for aseptic loosening with the CC genotype at highest risk for aseptic loosening, Odds Ratio CC vs. AA 1.93, 95%CI 1.15–3.25, p = 0.013. In contrast, low risk AA genotype carriers that still developed aseptic loosening showed a significantly shorter time to aseptic loosening than patients carrying the C allele (p = 0.004). These results indicate that the BCL2 -938C>A polymorphism influences the occurrence and course of aseptic loosening and suggests this polymorphism as an interesting candidate for prospective studies and analyses in THA registers. 相似文献
67.
Georg Wolff Christoph Hagen Kay Grünewald Rainer Kaufmann 《Biology of the cell / under the auspices of the European Cell Biology Organization》2016,108(9):245-258
Correlative light and electron microscopy (CLEM) has become a powerful tool in life sciences. Particularly cryo‐CLEM, the combination of fluorescence cryo‐microscopy (cryo‐FM) permitting for non‐invasive specific multi‐colour labelling, with electron cryo‐microscopy (cryo‐EM) providing the undisturbed structural context at a resolution down to the Ångstrom range, has enabled a broad range of new biological applications. Imaging rare structures or events in crowded environments, such as inside a cell, requires specific fluorescence‐based information for guiding cryo‐EM data acquisition and/or to verify the identity of the structure of interest. Furthermore, cryo‐CLEM can provide information about the arrangement of specific proteins in the wider structural context of their native nano‐environment. However, a major obstacle of cryo‐CLEM currently hindering many biological applications is the large resolution gap between cryo‐FM (typically in the range of ~400 nm) and cryo‐EM (single nanometre to the Ångstrom range). Very recently, first proof of concept experiments demonstrated the feasibility of super‐resolution cryo‐FM imaging and the correlation with cryo‐EM. This opened the door towards super‐resolution cryo‐CLEM, and thus towards direct correlation of structural details from both imaging modalities. 相似文献
68.
Maja?von der Hagen Julia?B.?Hennermann Horst?von Bernuth Birgit?Spors Angela?M.?KaindlEmail author 《Medizinische Genetik》2016,28(1):1-14
Microcephaly affects 2–3?% of the population and is often associated with intellectual disability. The underlying reduction in brain volume can result from various exogenous factors or genetic causes. Microcephaly remains a poorly defined condition lacking both uniform diagnostic approaches and classification. A definite etiological diagnosis is the key to predict the prognosis, identify co-morbidities and offer genetic counseling. In addition, the identification of the underlying cause increases our knowledge of brain development and the clinical spectrum of microcephaly. We propose a diagnostic approach for children with microcephaly from a pediatric neurologist point of view. 相似文献
69.
70.
Wang H Julenius K Hryhorenko J Hagen FK 《The Journal of biological chemistry》2007,282(19):14586-14597
Proteoglycan modification is essential for development and early cell division in Caenorhabditis elegans. The specification of proteoglycan attachment sites is defined by the Golgi enzyme polypeptide xylosyltransferase. Here we evaluate the substrate specificity of this xylosyltransferase for its downstream targets by using reporter proteins containing proteoglycan modification sites from C. elegans syndecan/SDN-1. The N terminus of the SDN-1 contains a Ser-Gly proteoglycan site at Ser(71), flanked by potential mucin and N-glycosylation sites. However, Ser(71) was exclusively used as a proteoglycan site in vivo, based on mapping studies with a Ser(71) reporter protein, glycosyltransferase RNA interference, and co-expression of worm polypeptide xylosyltransferase. To elucidate the substrate requirements of this enzyme, a library of 42 point mutants of the Ser(71) reporter was expressed in tissue culture. The nematode proteoglycan modification site in SDN-1 required serine (not threonine), two flanking glycine residues (positions -1 and +1), and either one proximal acidic N-terminal amino acid (positions -4, -3, and -2) or a pair of distal N-terminal acidic amino acids (positions -6 and -5). C-terminal acidic amino acids, although present in many proteoglycan modification sites, had minimal impact on xylosylation at Ser(71). Proline inhibited glycosylation when present at -1, +1, or +2. The position of glycine, proline, and acidic amino acids allows the glycosylation machinery to discriminate between mucin and proteoglycan modification sites. The key residues that define proteoglycan modification sites also function with the Drosophila polypeptide xylosyltransferase, indicating that the specificity in the glycosylation process is evolutionarily conserved. Using a neural network method, a preliminary proteoglycan predictor has been developed. 相似文献