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991.
A series of linear and angular prenylated furanocoumarins and a benzofuran derivative were isolated from leaves and twigs of Dorstenia gigas (Moraceae), a plant occurring endemically on Socotra Island (Yemen). The structures were elucidated by spectroscopic methods (NMR, MS, UV) and chemical derivatization. 相似文献
992.
993.
Haygood MG Schmidt EW Davidson SK Faulkner DJ 《Journal of molecular microbiology and biotechnology》1999,1(1):33-43
Marine invertebrates are sources of a diverse array of bioactive metabolites with great potential for development as drugs and research tools. In many cases, microorganisms are known or suspected to be the biosynthetic source of marine invertebrate natural products. The application of molecular microbiology to the study of these relationships will contribute to basic biological knowledge and facilitate biotechnological development of these valuable resources. The bryostatin-producing bryozoan B. neritina and its specific symbiont "Candidatus Endobugula sertula" constitute one promising model system. Another fertile subject for investigation is the listhistid sponges that contain numerous bioactive metabolites, some of which originate from bacterial symbionts. 相似文献
994.
Waldow A Schmidt B Dierks T von Bülow R von Figura K 《The Journal of biological chemistry》1999,274(18):12284-12288
Arylsulfatase A belongs to the sulfatase family whose members carry a Calpha-formylglycine that is post-translationally generated by oxidation of a conserved cysteine or serine residue. The formylglycine acts as an aldehyde hydrate with two geminal hydroxyls being involved in catalysis of sulfate ester cleavage. In arylsulfatase A and N-acetylgalactosamine 4-sulfatase this formylglycine was found to form the active site together with a divalent cation and a number of polar residues, tightly interconnected by a net of hydrogen bonds. Most of these putative active site residues are highly conserved among the eukaryotic and prokaryotic members of the sulfatase family. To analyze their function in binding and cleaving sulfate esters, we substituted a total of nine putative active site residues of human ASA by alanine (Asp29, Asp30, Asp281, Asn282, His125, His229, Lys123, Lys302, and Ser150). In addition the Mg2+-complexing residues (Asp29, Asp30, Asp281, and Asn282) were substituted conservatively by either asparagine or aspartate. In all mutants Vmax was decreased to 1-26% of wild type activity. The Km was more than 10-fold increased in K123A and K302A and up to 5-fold in the other mutants. In all mutants the pH optimum was increased from 4.5 by 0.2-0.8 units. These results indicate that each of the nine residues examined is critical for catalytic activity, Lys123 and Lys302 by binding the substrate and the others by direct (His125 and Asp281) or indirect participation in catalysis. The shift in the pH optimum is explained by two deprotonation steps that have been proposed for sulfate ester cleavage. 相似文献
995.
The hyperthermophilic archaeon Sulfolobus acidocaldarius exchanges and recombines chromosomal markers by a conjugational mechanism, and the overall yield of recombinants is greatly increased by previous exposure to UV light. This stimulation was studied in an effort to clarify its mechanism and that of marker exchange itself. A variety of experiments failed to identify a significant effect of UV irradiation on the frequency of cell pairing, indicating that subsequent steps are primarily affected, i.e., transfer of DNA between cells or homologous recombination. The UV-induced stimulation decayed rather quickly in parental cells during preincubation at 75 degrees, and the rate of decay depended on the incubation temperature. Preincubation at 75 degrees decreased the yield of recombinants neither from unirradiated parental cells nor from parental suspensions subsequently irradiated. We interpret these results as evidence that marker exchange is stimulated by recombinogenic DNA lesions formed as intermediates in the process of repairing UV photoproducts in the S. acidocaldarius chromosome. 相似文献
996.
Friedrich M Villena-Heinsen C Meyberg R Woll-Hermann A Reitnauer K Schmidt W Tilgen W Reichrath J 《The Histochemical journal》1999,31(11):717-722
The human Mut-S-Homologon-2 (hMSH-2) gene product is a member of a highly conserved family of proteins involved in postreplication mismatch repair. We have analysed hMSH-2 expression in normal ovarian tissue (n=15) and ovarian carcinomas (n=40). hMSH-2 protein was investigated immunohistochemically on frozen sections using a highly sensitive streptavidin–peroxidase technique and a specific mouse monoclonal antibody (clone FE11). A hMSH-2-immunoreactivity score (hMSH-2-IRS) for semiquantitative analysis of hMSH-2 expression is presented. In normal ovarian tissue, we only found weak nuclear immunoreactivity for hMSH-2 in 60%, while the remaining 40% were hMSH-2 negative (mean hMSH-2-IRS: 0.73; SD: ±0.70). All ovarian carcinomas analysed revealed moderate to strong nuclear immunoreactivity (mean hMSH-2-IRS: 8.05; SD: ±3.65). hMSH-2 staining was heterogeneous, with visual differences between individual tumour cells. Expression of hMSH-2 protein was consistently and strongly upregulated in tumour cells of ovarian carcinomas as compared to normal ovarian tissue. No statistically significant correlation in comparing the labelling patterns for hMSH-2 with the labelling patterns for Ki-67 (mean percentage of Ki-67 positive tumour cells: 25.88%; SD: ±18.43) was observed in ovarian carcinomas. Furthermore, no statistical significant correlations between hMSH-2-IRS and histological grading (p=0.47), histological type of carcinoma (p=0.706) or FIGO-classification (p=0.054) were found. Our findings indicate that (a) hMSH-2 is expressed in normal human ovarian tissue, (b) expression of hMSH-2 is increased in ovarian carcinomas, (c) expression of hMSH-2 may be of importance for the genetic stability of ovarian carcinomas in vivo, (d) hMSH-2 mutations may not cause microsatellite instability in ovarian carcinomas, (e) hMSH-2 may contribute to mechanisms responsible for resistance to anticancer drugs. 相似文献
997.
Evidence is presented for the existence of a Venturia homologue of hemomucin, a surface mucin that was recently described in Drosophila. Venturia hemomucin is part of the mucinous layer on the egg and larval surface of the parasitoid. Venturia hemomucin forms a complex with lipophorin and other host hemolymph components, that is similar to a hemomucin-lipophorin complex which is part of the coagulation reaction. The possible formation of a specific layer against the host defence system is discussed for eggs and larvae that develop inside another insect. 相似文献
998.
Steinhoff M McGregor GP Radleff-Schlimme A Steinhoff A Jarry H Schmidt WE 《Regulatory peptides》1999,80(1-2):49-55
Morphological and biochemical evidence is presented for the presence of pituitary adenylate cyclase activating peptide (PACAP) and the high-affinity PACAP-1 receptor subtype in human skin. Immunohistochemical analysis revealed PACAP-immunoreactivity (IR) to be present predominantly in dermal nerve fibers close to the dermal-epidermal border, hair follicles, blood vessels and sweat glands. Radioimmunoassay, chromatographic analysis and Western blotting revealed this PACAP-IR to be PACAP-38 whereas the second molecular form, PACAP-27, is absent. In tissue of psoriasis patients significantly more PACAP-38 protein was detected as compared to normal skin. Using RT-PCR, the expression of a high-affinity PACAP-1 receptor in human skin was observed. These results indicate a possible role for PACAP-38 in inflammatory processes of psoriasis. 相似文献
999.
Schmidt O Theopold U 《BioEssays : news and reviews in molecular, cellular and developmental biology》2004,26(12):1344-1350
The cellular capacity to internalise objects, involving attachment, engulfment and uptake, exists in virtually all organisms. Many uptake reactions are associated with cell signalling. However, the mechanical forces that form endocytotic vesicles are not known. We propose a 'leverage-mediated' uptake mechanism involving lateral cross-linking processes on the cell surface that can generate the configurational energy to create an inverse curvature of the membrane. 相似文献
1000.
Inhibitors that are structurally related to the transition-state model of the proposed SN1-type mechanism of sialyl transfer, exhibit particularly high binding affinities to alpha(2-6)sialyltransferases. Furthermore, replacing the neuraminyl residue with a simple aryl or hetaryl ring and substituting the carboxylate group for a phosphonate moiety, improves both binding affinity and synthetic accessibility. Herein we report on the synthesis and inhibition of a wide range of novel, potent transition-state analogue based alpha(2-6)sialyltransferase inhibitors comprising a planar anomeric carbon, an increased distance between the anomeric carbon and the CMP leaving group, and at least two negative charges. We also present a short, efficient asymmetric synthesis of the most promising benzyl inhibitors, providing rapid access to large quantities of highly potent, stereochemically-pure (>96% de) inhibitors for further biological investigation (e.g.(R)-3b, Ki = 70 nM). 相似文献