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131.
Discovery and structural characterization of an allosteric inhibitor of bacterial cis‐prenyltransferase 下载免费PDF全文
Dennis E. Danley Eric T. Baima Mahmoud Mansour Kimberly F. Fennell Boris A. Chrunyk John P. Mueller Shenping Liu Xiayang Qiu 《Protein science : a publication of the Protein Society》2015,24(1):20-26
Undecaprenyl pyrophosphate synthase (UPPs) is an essential enzyme in a key bacterial cell wall synthesis pathway. It catalyzes the consecutive condensations of isopentenyl pyrophosphate (IPP) groups on to a trans-farnesyl pyrophosphate (FPP) to produce a C55 isoprenoid, undecaprenyl pyrophosphate (UPP). Here we report the discovery and co-crystal structures of a drug-like UPPs inhibitor in complex with Streptococcus pneumoniae UPPs, with and without substrate FPP, at resolutions of 2.2 and 2.1 Å, respectively. The UPPs inhibitor has a low molecular weight (355 Da), but displays potent inhibition of UPP synthesis in vitro (IC50 50 nM) that translates into excellent whole cell antimicrobial activity against pathogenic strains of Streptococcal species (MIC90 0.4 µg mL−1). Interestingly, the inhibitor does not compete with the substrates but rather binds at a site adjacent to the FPP binding site and interacts with the tail of the substrate. Based on the structures, an allosteric inhibition mechanism of UPPs is proposed for this inhibitor. This inhibition mechanism is supported by biochemical and biophysical experiments, and provides a basis for the development of novel antibiotics targeting Streptococcus pneumoniae. 相似文献
132.
Mojtaba Sankian Abdolreza Varasteh Nazanin Pazouki Mahmoud Mahmoudi 《Clinical and molecular allergy : CMA》2005,3(1):1-9
Background
The basophil activation test (BAT), in which translocation of markers to the surface of blood basophils is measured in response to allergen by flow cytometry, is a rapid assay that is gaining popularity. Two markers are currently being evaluated for the BAT; CD63 and the lineage-specific CD203c. In a recent report, detection of CD203c after lysis with Saponin was shown to be superior to detection of CD63 after lysis with formic acid. We wanted to compare a) lysis with formic acid and lysis with Saponin, b) the response through CD203c and CD63, and c) the definition 10% activated cells above background with the probability binning metric T(χ) > 4, on sets of data generated with blood basophils stimulated with varying concentrations of anti-FcεRI antibody.Methods
Blood from volunteers was incubated with serial logarithmic dilutions of anti-FcεRI and subsequently with antibodies to CD203c PE and CD63 FITC. Sets of samples set up in parallel were lysed with either Saponin based Whole Blood Lysing reagent or with formic acid based Immunoprep/Q-prep. Samples were acquired on a FACS Calibur, but were compensated and analysed offline. Responders were defined as persons who had 10% or more activated basophils above background, or a T(χ) > 4, for two consecutive dilutions of anti-FcεRI antibody.Results
More basophils (median 1164 vs. median 397) and better discrimination of upregulated CD203c and CD63 amongst responders were obtained after lysis with Saponin than after lysis with formic acid. We suggest that CD203c may be a more sensitive marker for the BAT than CD63, as 6/11 responders were found with CD203c, compared with 3/11 with CD63. Most responders (7/11) were identified with probability binning.Conclusion
A combination of lysis with Saponin and the markers CD203c and CD63 computed by probability binning may be the most sensitive method of detecting activation of basophils after stimulation through FcεRI. 相似文献133.
A validated, simple and sensitive HPLC method was developed for the simultaneous determination of lipoperoxidation relevant reactive aldehydes: glyoxal (GO), acrolein (ACR), malondialdehyde (MDA), and 4-hydroxy-2-nonenal (HNE) in human serum. The studied aldehydes were reacted with 2,2′-furil to form fluorescent difurylimidazole derivatives that were separated on a C18 column using gradient elution and fluorescence detection at excitation and emission wavelengths of 250 and 355 nm, respectively. The method showed good linearity over the concentration ranges of 0.100–5.00, 0.200–10.0, 0.200–40.0, and 0.400–10.0 nmol/mL for GO, ACR, HNE, and MDA, respectively, with detection limits ranging from 0.030 to 0.11 nmol/mL. The percentage RSD of intraday and interday precision did not exceed 5.0 and 6.2%, respectively, and the accuracy (%found) ranged from 95.5 to 103%. The proposed method was applied for monitoring the four aldehydes in sera of healthy, diabetic, and rheumatic human subjects with simple pretreatment steps and without interference from endogenous components. By virtue of its high sensitivity and accuracy, our method enabled detection of differences between analytes concentrations in sera of human subjects under different clinical conditions. 相似文献
134.
David Julian Arias-Chávez Patrick Mailloux-Salinas Jessica Ledesma Aparicio Elihu Campos-Pérez Omar Noel Medina-Campos José Pedraza-Chaverri Guadalupe Bravo 《Journal of cellular and molecular medicine》2023,27(20):3147-3156
Benign prostatic hyperplasia (BPH) is the most common adenoma in old men. Tomatoes are a rich source of bioactive compounds that, as well as selenium (Se), possess antioxidant and antiproliferative activity. The aim was to evaluate the therapeutic effect of Se in combination with a tomato extract in aged rats with BPH. Aged male Wistar rats were divided in the following groups (n = 10 rats/group): Control (C), BPH, BPH + Finasteride (BPH + F), BPH + Tomato Lipidic Extract (BPH + E), BPH + Selenium (BPH + S) and BPH plus E plus S (BPH + E + S). After 4 weeks of treatment, prostate weight, diuresis, antioxidants enzymes, prooxidants and inflammatory markers, growth factors and androgens were determined. BPH + E + S reduced prostate weight by 59.29% and inhibited growth by 99.35% compared to BPH + F which only decreased weight and inhibited growth by 15.31% and 57.54%, respectively. Prooxidant markers were higher with BPH + F (49.4% higher vs. BPH), but BPH + E + S decreased these markers (94.27% vs. BPH) and increased antioxidant activity. Finally, diuresis was higher with the BPH + E + S combination and markers of inflammation and growth factors were significantly lower with respect to BPH + F. Our findings provide a beneficial and protective therapeutic option of E + S directed against androgens, oxidative stress and inflammation that regulates cell proliferation in the prostate gland. 相似文献
135.
The geography of snake reproductive mode: a global analysis of the evolution of snake viviparity 下载免费PDF全文
136.
Neven Makram Aziz Merhan Mamdouh Ragy Sabreen Mahmoud Ahmed 《Cell stress & chaperones》2018,23(6):1237-1245
The aim of this study is to investigate the effect of somatostatin (SST) analogue, Octreotide, on some features of liver injury induced by immobilization stress (IS) in adult male albino rats. Eighteen adult male albino rats were randomly divided into three equal groups: control, IS, and Octreotide-treated stressed groups. Octreotide (40 μg/kg body weight, subcutaneously) was administrated twice daily for 8 days during the exposure to IS. Octreotide was found to reduce the IS significantly and induce elevations in the plasma level of corticosterone, liver transaminases, and tumor necrosis factor α (TNF-α) as compared with IS group. Furthermore, Octreotide administration has significantly elevated the decline in the total antioxidant capacities (TAC) and lowered the elevated malondialdehyde (MDA) levels observed with IS in the hepatic tissue. Additionally, Octreotide treatment provided protection against the histopathological changes in the stressed liver in the form of significant reduction in the mean number of degenerated hepatocytes, the area % of collagen fibers, and glial fibrillary acid protein (GFAP) immunostaining with a significant increase in the mean number of normal hepatocytes. In conclusion, stressed rats showed disturbed liver functions and its oxidant–antioxidant status with highly expression hepatic stellate cells (HSCs), which were all improved by Octreotide administration, SST analogue. 相似文献
137.
Omar Bagasra Bernice M. Eppright Ivan Damjanov 《Cancer immunology, immunotherapy : CII》1998,15(1):27-31
Summary A latex bead technique modified for measuring the plaque-forming cell (PFC) response to teratocarcinoma tumor antigens in syngeneic animals is described.With this method one can detect both the primary (IgM) and the secondary (IgG) immune response to tumor antigens. Optimal detection of the PFC response depends on the proper ratio of sheep red blood cells to latex beads and the dose of tumor cell antigen used for immunization. The presence of fetal calf serum interfered with immunization of animals and the coating of the latex beads with the tumor cell antigens. The plaques obtained in response to immunization with teratocarcinoma cell antigens varied in size, probably reflecting the complex immune response to more than one class of antigens on tumor cells. 相似文献
138.
Abdel-Halim Mahmoud Mohammed El-Sayed Hans Jürgen Rehm 《Applied microbiology and biotechnology》1987,26(3):211-214
Summary The growth rates of immobilized Penicillium chrysogenum strains are important in their application to semicontinuous penicillin production. Immobilized P. chrysogenum strains produced about 10–15% less biomass but about 1–2 times more penicillin than free suspended mycelia.In a chemically defined medium an industrial P. chrysogenum strain, S1, produced about 10–12 times more penicillin than strain ATCC 12690. In a complex medium the immobilized P. chrysogenum S1 produced about 12% penicillin more than in shaken cultures. In bubble column fermentations, penicillin production was 163% higher in the complex medium than in the chemically defined medium. 相似文献
139.
Mahmoud A. Ibrahim Abdel-Hady M. Ghazy Tahany M. Maharem Mohamed I. Khalil 《Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology》2001,130(4)
An inhibitor of factor Xa (FXa) was isolated from the nymphs of the camel tick Hyalomma dromedarii by a combination of chromatography on DEAE-cellulose and Sephacryl S-300 columns. The isolated nymphal FXa inhibitor turned out to be a homogenous preparation of a single polypeptide chain (15 kDa) as judged by both the native and denatured SDS-PAGE. Its pI value ranged from 7.7 to 7.9. The inhibitor is a potent anticoagulant since it prolonged both the activated partial thromboplastin time (APTT) and the prothrombin time (PT) of the camel plasma in a concentration-dependent manner. Its activity was threefold lower toward thrombin than FXa, but it did not inhibit any of the proteases; trypsin, α-chymotrypsin, papain, pepsin and subtilisin. The inhibitor binds at two sites on FXa uncompetitively with an inhibition constant (Ki) value of 134 nM. 相似文献
140.
deMello DE Mahmoud S Padfield PJ Hoffmann JW 《In vitro cellular & developmental biology. Animal》2000,36(6):374-382
Summary This paper describes a new fully differentiated Type-II alveolar epithelial cell line designated T7, derived from transgenic H-2Kb-tsA58 mice, capable of being passaged as an immortalized cloned cell line in culture. H-2Kb-tsA58 mice harbor a temperature-sensitive (ts) mutant of the simian virus 40 (SV40) large tumor antigen (T antigen) under
the control of the γ-interferon (INF)-inducible mouse major histocompatibility complex H-2Kb promoter. When cultured under permissive conditions (33°C and in the presence of γ-INF) cells isolated from H-2Kb-tsA58 mice express the large T antigen, which drives the cells to proliferate. However, upon withdrawal of the γ-INF and
transfer of the cells to a higher temperature (39°C), T antigen expression is turned off, the cells stop proliferating and
differentiate. The T7 cell line is a clonal cell line originally derived from a Type-II cell-rich fraction isolated from lungs of H-2Kb-tsA58 mice. The T7 cells form confluent monolayers, and have a polarized epithelial cell morphology with tight junctions and apical microvilli.
In addition, the T7 cells have distinct cytoplasmic lamellar bodies, which become more numerous and pronounced when the cells are grown under
nonpermissive conditions. The T7 cells synthesize and secrete phosphatidylcholine and the three surfactant proteins, SP-A, SP-B, and SP-C. The T7 cell line is unique in that it is the first non-tumor-derived Type-II cell line capable of synthesizing and secreting the
major components of surfactant. Based on the criteria studied, the T7 cell line is phenotypically very similar to normal Type-II cells. The T7 cell line, therefore, should prove a valuable experimental system to advance the study of the cell biology/physiology of
surfactant metabolism and secretion as well as serve as a model for other studies of Type-II cell physiology. 相似文献