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1.
Bo Ram Kim Ji-Young Park Hyung Jae Jeong Hyung-Jun Kwon Su-Jin Park In-Chul Lee 《Journal of enzyme inhibition and medicinal chemistry》2018,33(1):1256-1265
Sialidases are key virulence factors that remove sialic acid from the host cell surface glycan, unmasking receptors that facilitate bacterial adherence and colonisation. In this study, we developed potential agents for treating bacterial infections caused by Streptococcus pneumoniae Nan A that inhibit bacterial sialidase using Turmeric and curcumin analogues. Design, synthesis, and structure analysis relationship (SAR) studies have been also described. Evaluation of the synthesised derivatives demonstrated that compound 5e was the most potent inhibitor of S. pneumoniae sialidase (IC50?=?0.2?±?0.1?µM). This compound exhibited a 3.0-fold improvement in inhibitory activity over that of curcumin and displayed competitive inhibition. These results warrant further studies confirming the antipneumococcal activity 5e and indicated that curcumin derivatives could be potentially used to treat sepsis by bacterial infections. 相似文献
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The crystal structure of a complex between DNase I and the self-complementary octamer duplex d(GGTATACC)2 has been solved using the molecular replacement method and refined to a crystallographic R-factor of 18.8% for all data between 6.0 and 2.3 A resolution. In contrast to the structure of the DNase I-d(GCGATCGC)2 complex solved previously, the DNA remains uncleaved in the crystal. The general architecture of the two complexes is highly similar. DNase I binds in the minor groove of a right-handed DNA duplex, and to the phosphate backbones on either side over five base-pairs, resulting in a widening of the minor groove and a concurrent bend of the DNA away from the bound enzyme. There is very little change in the structure of the DNase I on binding the substrate. Many other features of the interaction are conserved in the two complexes, in particular the stacking of a deoxyribose group of the DNA onto the side-chain of a tyrosine residue (Y76), which affects the DNA conformation and the binding of an arginine side-chain in the minor groove. Although the structures of the DNA molecules appear at first sight rather similar, detailed analysis reveals some differences that may explain the relative resistance of the d(GGTATACC)2 duplex to cleavage by DNase I: whilst some backbone parameters are characteristic of a B-conformation, the spatial orientation of the base-pairs in the d(GGTATACC)2 duplex is close to that generally observed in A-DNA. These results further support the hypothesis that the minor-groove width and depth and the intrinsic flexibility of DNA are the most important parameters affecting the interaction. The disposition of residues around the scissile phosphate group suggests that two histidine residues, H134 and H252, are involved in catalysis. 相似文献
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Summary The cloning of glucoamylase geneSTA using theSUC2 promoter intoSaccharomyces cerevisiae was performed. The signal sequence ofSTA gene was used for the secretion of glucoamylase protein. The plasmid constructed in this way was named YEpSUCSTA and its expression was identified. The expression of YEpSUCSTA was repressed in the presence of glucose in growth medium, but derepressed when glucose became depleted. YEpSUCSTA showed the similar efficiency of glucoamylase secretion as YEpSTA-F which has the entireSTA gene. Glucoamylase activity in starch-glucose medium was largely increased because cell mass and plasmid stability were high in biosynthesis phase compared to extracellular glucoamylase activities in media which starch or glucose was the only carbon source. 相似文献
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Prostaglandin H Synthetase-Mediated Metabolism of Dopamine: Implication for Parkinson's Disease 总被引:2,自引:1,他引:1
† Michael B. Mattammal ‡§Randy Strong †Vijaya M. Lakshmi ¶Hyung D. Chung #Alan H. Stephenson 《Journal of neurochemistry》1995,64(4):1645-1654
Abstract: Differences in prostaglandin H synthetase (PHS) activity in the substantia nigra of age- and post-mortem interval-matched parkinsonian, Alzheimer's, and normal control brain tissue were assessed. Prostaglandin E2 (PGE2 , an index of PHS activity) was higher in substantia nigra of parkinsonian brain tissue than Alzheimer's or control tissue. Incubation of substantia nigra slices with arachidonic acid (AA) increased PGE2 synthesis. Dopamine stimulated PHS synthesis of PGE2 . [3 H]Dopamine was activated by PHS to electrophilic intermediate(s) that covalently bound to DNA, microtubulin protein, bovine serum albumin, and sulfhydryl reagents. When AA was replaced by hydrogen peroxide, PHS/H2 O2 -supported binding proceeded at rates similar to those observed with PHS/AA. Indomethacin and aspirin inhibited AA-mediated cooxidation of dopamine but not H2 O2 -mediated metabolism. PHS-mediated metabolism of dopamine was not affected by monoamine oxidase inhibitors. Substrate requirements and effects of specific inhibitors suggest cooxidation of dopamine is mediated by the hydroperoxidase activity of PHS. 32 P-postlabeling was used to detect dopamine-DNA adducts. PHS/AA activation of dopamine in the presence of DNA resulted in the formation of five dopamine-DNA adducts, i.e., 23, 43, 114, 70, and 270 amol/µg DNA. DNA adduct formation was PHS, AA, and dopamine dependent. PHS catalyzed cooxidation of dopamine in dopaminergic neuronal degeneration is discussed. 相似文献
7.
Centromere-Linkage Analysis and Consolidation of the Zebrafish Genetic Map 总被引:17,自引:2,他引:15 下载免费PDF全文
S. L. Johnson M. A. Gates M. Johnson W. S. Talbot S. Horne K. Baik S. Rude J. R. Wong J. H. Postlethwait 《Genetics》1996,142(4):1277-1288
The ease of isolating mutations in zebrafish will contribute to an understanding of a variety of processes common to all vertebrates. To facilitate genetic analysis of such mutations, we have identified DNA polymorphisms closely linked to each of the 25 centromeres of zebrafish, placed centromeres on the linkage map, increased the number of mapped PCR-based markers to 652, and consolidated the number of linkage groups to the number of chromosomes. This work makes possible centromere-linkage analysis, a novel, rapid method to assign mutations to a specific linkage group using half-tetrads. 相似文献
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Hyung Soo Park Byung Hong Kim Hyo Suk Kim Hyung Joo Kim Gwang Tae Kim Mia Kim In Seop Chang Yong Keun Park Hyo Ihl Chang 《Anaerobe》2001,7(6):297
An obligatory anaerobic bacterium was isolated from a mediator-less microbial fuel cell using starch processing wastewater as the fuel and designated as EG3. The isolate was Gram-positive, motile and rod (2.8–3.0 μm long, 0.5–0.6 μm wide). The partial 16S rRNA gene sequence and analysis of the cellular fatty acids profile suggested that EG3 clusters with Clostridium sub-phylum and exhibited the highest similarity (98%) with Clostridium butyricum. The temperature and pH optimum for growth were 37°C and 7.0, respectively. The major products of glucose and glucose/Fe(O)OH metabolism were lactate, formate, butyrate, acetate, CO2and H2. Growth was faster at the initial phase and the cell yield was higher when the medium was supplemented with Fe(O)OH than without Fe(O)OH. These results suggest that Fe(III) ion is utilised as an electron sink. Cyclic voltammetry showed that Clostridium butyricum EG3 cells were electrochemically active. It is a novel characteristic of strict anaerobic Gram-positive bacteria. 相似文献
10.
Bang Wool Eom Keun Won Ryu Byung-Ho Nam Yunjin Park Hyuk-Joon Lee Min Chan Kim Gyu Seok Cho Chan Young Kim Seung Wan Ryu Dong Woo Shin Woo Jin Hyung Jun Ho Lee 《PloS one》2015,10(2)
BackgroundA small number of nomograms have been previously developed to predict the individual survival of patients who undergo curative resection for gastric cancer. However, all were derived from single high-volume centers. The aim of this study was to develop and validate a nomogram for gastric cancer patients using a multicenter database.MethodsWe reviewed the clinicopathological and survival data of 2012 patients who underwent curative resection for gastric cancer between 2001 and 2006 at eight centers. Among these centers, six institutions were randomly assigned to the development set, and the other two centers were assigned to the validation set. Multivariate analysis using the Cox proportional hazard regression model was performed, and discrimination and calibration were evaluated by external validation.ResultsMultivariate analyses revealed that age, tumor size, lymphovascular invasion, depth of invasion, and metastatic lymph nodes were significant prognostic factors for overall survival. In the external validation, the concordance index was 0.831 (95% confidence interval, 0.784–0.878), and Hosmer-Lemeshow chi-square statistic was 3.92 (P = 0.917).ConclusionsWe developed and validated a nomogram to predict 5-year overall survival after curative resection for gastric cancer based on a multicenter database. This nomogram can be broadly applied even in general hospitals and is useful for counseling patients, and scheduling follow-up. 相似文献