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41.
Theoretical investigation on the glycan‐binding specificity of Agrocybe cylindracea galectin using molecular modeling and molecular dynamics simulation studies
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Ponnusamy Parasuraman Veeramani Murugan Jeyasigamani F A Selvin M Michael Gromiha Kazuhiko Fukui Kasinadar Veluraja 《Journal of molecular recognition : JMR》2015,28(9):528-538
Galectins are β‐galactoside binding proteins which have the ability to serve as potent antitumor, cancer biomarker, and induce tumor cell apoptosis. Agrocybe cylindracea galectin (ACG) is a fungal galectin which specifically recognizes α(2,3)‐linked sialyllactose at the cell surface that plays extensive roles in the biological recognition processes. To investigate the change in glycan‐binding specificity upon mutations, single point and double point site‐directed in silico mutations are performed at the binding pocket of ACG. Molecular dynamics (MD) simulation studies are carried out for the wild‐type (ACG) and single point (ACG1) and double point (ACG2) mutated ACGs to investigate the dynamics of substituted mutants and their interactions with the receptor sialyllactose. Plausible binding modes are proposed for galectin–sialylglycan complexes based on the analysis of hydrogen bonding interactions, total pair‐wise interaction energy between the interacting binding site residues and sialyllactose and binding free energy of the complexes using molecular mechanics–Poisson–Boltzmann surface area. Our result shows that high contribution to the binding in different modes is due to the direct and water‐mediated hydrogen bonds. The binding specificity of double point mutant Y59R/N140Q of ACG2 is found to be high, and it has 26 direct and water‐mediated hydrogen bonds with a relatively low‐binding free energy of −47.52 ± 5.2 kcal/mol. We also observe that the substituted mutant Arg59 is crucial for glycan‐binding and for the preference of α(2,3)‐linked sialyllactose at the binding pocket of ACG2 galectin. When compared with the wild‐type and single point mutant, the double point mutant exhibits enhanced affinity towards α(2,3)‐linked sialyllactose, which can be effectively used as a model for biological cell marker in cancer therapeutics. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
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43.
Enhancement of the anti‐inflammatory activity of temporin‐1Tl‐derived antimicrobial peptides by tryptophan,arginine and lysine substitutions
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Ganesan Rajasekaran Radhakrishnan Kamalakannan Song Yub Shin 《Journal of peptide science》2015,21(10):779-785
Temporin‐1Tl (TL) is a 13‐residue frog antimicrobial peptide (AMP) exhibiting potent antimicrobial and anti‐inflammatory activity. To develop novel AMP with improved anti‐inflammatory activity and antimicrobial selectivity, we designed and synthesized a series of TL analogs by substituting Trp, Arg and Lys at selected positions. Except for Escherichia coli and Staphylococcus epidermidis, all TL analogs exhibited retained or increased antimicrobial activity against seven bacterial strains including three methicillin‐resistant Staphylococcus aureus strains compared with TL. TL‐1 and TL‐4 showed a little increase in antimicrobial selectivity, while TL‐2 and TL‐3 displayed slightly decreased antimicrobial selectivity because of their about twofold increased hemolytic activity. All TL analogs demonstrated greatly increased anti‐inflammatory activity, evident by their higher inhibition of the production tumor necrosis factor‐α (TNF‐α) and nitric oxide and the mRNA expression of inducible nitric oxide synthase and TNF‐α in lipopolysaccharide (LPS)‐stimulated RAW264.7 macrophage cells, compared with TL. Taken together, the peptide anti‐inflammatory activity is as follows: TL‐2 ≈ TL‐3 ≈ TL‐4 > TL‐1 > TL. In addition, LPS binding ability of the peptides corresponded with their anti‐inflammatory activity. These results apparently suggest that the anti‐inflammatory activity of TL analogs is associated with the direct binding ability between these peptides and LPS. Collectively, our designed TL analogs possess improved anti‐inflammatory activity and retain antimicrobial activity without a significant increase in hemolysis. Therefore, it is evident that our TL analogs constitute promising candidates for the development of peptide therapeutics for gram‐negative bacterial infection. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
44.
K. Murugan K. Selvanayaki Saleh Al-Sohaibani 《World journal of microbiology & biotechnology》2011,27(7):1661-1668
Respiratory tract and device associated infections caused by biofilm forming Pseudomonas aeruginosa play a primary role in the pathogenesis and prognosis of cystic fibrosis (CF) diseases. The biofilm formed by these pathogens
attributes to the antibiotic resistance and protection from host immune response. Once established, the pathogens respond
poorly to therapeutic agents. Recently medicinal plants are largely explored as potential source of bioactive agents. In this
context the present study reports the antibiofilm activity of the folkloric medicinal plant Andrographis paniculata against biofilm forming CF causative Pseudomonas aeruginosa isolated from CF sputum. P. aeruginosa was also assessed for their growth and development of the biofilm, phylogenetic relationship and antibiotic susceptibility.
Antibiogram of the strains indicated that they were resistant to more than one antibiotic. Six extracts of A. paniculata showed significant antibiofilm activity. P. aeruginosa strains, KMS P03 and KMS P05, were found to be maximally inhibited by the methanol extract to an extent of 88.6 and 87.5%
respectively. This is the first report on antibiofilm activity of A. paniculata extracts, and our results indicate scope for development of complementary medicine for biofilm associated infections. 相似文献
45.
Mason T. MacDonald Rajasekaran R. Lada Martine Dorais Steeve Pepin 《Trees - Structure and Function》2011,25(5):947-952
Post-harvest needle loss is a major problem for balsam fir and other Christmas tree species. Recent evidence has implicated
ethylene as a signal responsible for post-harvest needle abscission, but enzymological changes remain unknown. The objective
of this study was to identify and quantify cellulase activity associated with endogenous and exogenous ethylene-induced abscission.
An experiment was designed with three treatments (control, endogenous ethylene, or exogenous ethylene) with five replicates.
Key response variables include needle retention duration, xylem pressure potential, ethylene evolution rate, and cellulase
activity. Two complimentary methods were used to assess cellulase activity: a cellulose plate digestion and zymography. The
results confirm ethylene as a signal for post-harvest abscission and identify ethylene-induced cellulase. Ethylene evolution
was typically between 15 and 16 μL g−1 h−1, but there was no difference among the three treatments. However, exogenous ethylene significantly decreased needle retention
by 60% and resulted in a sixfold decrease in xylem pressure potential. In addition, cellulase activity increased by 8- and
12-fold in endogenous and exogenous ethylene-induced abscission, respectively, compared to the control. Identification of
ethylene-induced cellulase activity has increased our understanding of the post-harvest needle abscission process and confirms
ethylene’s role as a signal molecule. 相似文献
46.
Kim G Rajasekaran SA Thomas G Rosen EA Landaw EM Shintaku P Lassman C Said J Rajasekaran AK 《Histology and histopathology》2005,20(1):35-44
Junctional complexes such as tight junctions, adherens junctions, and desmosomes play crucial roles in the structure and function of epithelial cells. These junctions are involved in increasing cell-cell contact and as well serve as signaling centers regulating multiple functions in epithelial cells. Carcinoma cell lines cultured in the laboratory generally lack junctional complexes. However, studies directed towards understanding the distribution of junctional complexes in human cancer tissues are lacking. In this study, we analyzed by electron microscopy the distribution of junctional complexes in patients diagnosed with renal clear-cell carcinoma. We found that both tight junctions and adherens junctions were drastically reduced in patients with cancer compared to normal tissues. Desmosomes were not detected in normal proximal tubules while distinctly present in cancer tissues. These results suggest that analysis of junctional complexes in human tumors should provide valuable information that might have prognostic and diagnostic value. 相似文献
47.
Mineral contents of Aloe vera leaf gel and their role on streptozotocin-induced diabetic rats 总被引:1,自引:0,他引:1
The role of some inorganic elements like vanadium, zinc, sodium, potassium, calcium, copper, manganese, and traces of chromium
in the improvement of impaired glucose tolerance and their indirect role in the management of diabetes mellitus are being
increasingly recognized. In traditional methods, medicinal plants are being used, which contain both organic and inorganic
constituents. In the present study, an attempt has been made to analyze the inorganic elements present in Aloe vera leat gel and their role on diabetes-related biochemical alterations in experimental rats. Special emphasis was given to the
inorganic parts by carefully preparing ash of the leaf gel. The results clearly indicate the presence of several hypoglycemic-activity-possessing
elements in the gel. The ash treatment also resulted in hypoglycemic action. In conclusion, the presence of various inorganic
trace elements in the gel might account for the hypoglycemic nature of the plant. 相似文献
48.
Analysis of Loss of heterozygosity and immunohistochemistry in BRCA1 gene in sporadic breast cancers
Dinesh KP Devaraj H Murugan V Rajaraman R Niranjali S 《Molecular and cellular biochemistry》2006,287(1-2):177-183
BRCA1 is a tumour suppressor gene (TSG), which predisposes cancer to both breast and ovary. The primary objective of the present study is to ascertain the involvement of BRCA1 gene in the pathogenesis of sporadic breast cancer women in Chennai (South India) by analysing its protein expression by immunohistochemistry (IHC) and loss of heterozygosity (LOH) for confirmation of the involvement of TSG in the study population. We found down regulation of BRCA1 protein (54%) in IHC and it was correlated with the clinicopathological parameters of the patients. We found near significant correlation (P < 0.063) between BRCA1 protein expression and clinicopathological parameters. We found 30% LOH in our study and it was also correlated with the clinicopathological parameters. No correlation was found between LOH and clinicopathological parameters. Though we found no correlation, the results revealed in this study support the involvement of BRCA1 TSG in the pathogenesis of sporadic breast cancer women in Chennai (South India). 相似文献
49.
Murugan R 《Biophysical chemistry》2006,120(2):143-147
Interaction of a protein molecule with a specific-site on the DNA lattice can be modeled as an unbiased random jump process. Here we show that there exists a critical jump size (kc) beyond which site-specific association of a protein molecule with a DNA lattice cannot be facilitated. The maximum achievable association rate is predicted to be approximately 10(10) mol-1 s-1. This critical jump size scales with the total length of DNA lattice (N) as kc proportional, variantN2/3. Beyond kc the mean first passage time MFPT (denoted as T) required for the protein molecule to target the specific-site follows a linear scaling law as T proportional, variantN rather than the usual T proportional, variantN2 scaling law. On the basis of these results we argue that the evolution of the super coiled structures of the genomic DNA must be a consequence of the existence of this critical jump sizes. We finally show that the random jump method of searching for the specific-site by the protein molecule on the DNA lattice itself introduce an abstract linear type potential favoring the site-specific association rate. 相似文献
50.