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排序方式: 共有250条查询结果,搜索用时 31 毫秒
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Sekar P. Chandra Rajasekaran R. 《International journal of peptide research and therapeutics》2021,27(2):1043-1056
International Journal of Peptide Research and Therapeutics - Initial phase of COVID-19 infection is associated with the binding of viral spike protein S1 receptor binding domain (RBD) with the host... 相似文献
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C. George Priya Doss B. Rajith R. Rajasekaran Jain Srajan N. Nagasundaram C. Debajyoti 《Cell biochemistry and biophysics》2013,67(3):1307-1318
Polymorphisms in the human prion proteins lead to amino acid substitutions by the conversion of PrPC to PrPSc and amyloid formation, resulting in prion diseases such as familial Creutzfeldt–Jakob disease, Gerstmann–Straussler–Scheinker disease and fatal familial insomnia. Cation–π interaction is a non-covalent binding force that plays a significant role in protein stability. Here, we employ a novel approach by combining various in silico tools along with molecular dynamics simulation to provide structural and functional insight into the effect of mutation on the stability and activity of mutant prion proteins. We have investigated impressions of prevalent mutations including 1E1S, 1E1P, 1E1U, 1E1P, 1FKC and 2K1D on the human prion proteins and compared them with wild type. Structural analyses of the models were performed with the aid of molecular dynamics simulation methods. According to our results, frequently occurred mutations were observed in conserved sequences of human prion proteins and the most fluctuation values appear in the 2K1D mutant model at around helix 4 with residues ranging from 190 to 194. Our observations in this study could help to further understand the structural stability of prion proteins. 相似文献
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Anjana Singh Narendiran Rajasekaran Bettina Hartenstein Sibylle Szabowski Mieczyslaw Gajda Peter Angel Rolf Br?uer Harald Illges 《Arthritis research & therapy》2013,15(6):R222
Introduction
Matrix metalloproteinases (MMPs) are important in tissue remodelling. Here we investigate the role of collagenase-3 (MMP-13) in antibody-induced arthritis.Methods
For this study we employed the K/BxN serum-induced arthritis model. Arthritis was induced in C57BL/6 wild type (WT) and MMP-13-deficient (MMP-13–/–) mice by intraperitoneal injection of 200 μl of K/BxN serum. Arthritis was assessed by measuring the ankle swelling. During the course of the experiments, mice were sacrificed every second day for histological examination of the ankle joints. Ankle sections were evaluated histologically for infiltration of inflammatory cells, pannus tissue formation and bone/cartilage destruction. Semi-quantitative PCR was used to determine MMP-13 expression levels in ankle joints of untreated and K/BxN serum-injected mice.Results
This study shows that MMP-13 is a regulator of inflammation. We observed increased expression of MMP-13 in ankle joints of WT mice during K/BxN serum-induced arthritis and both K/BxN serum-treated WT and MMP-13–/– mice developed progressive arthritis with a similar onset. However, MMP-13–/– mice showed significantly reduced disease over the whole arthritic period. Ankle joints of WT mice showed severe joint destruction with extensive inflammation and erosion of cartilage and bone. In contrast, MMP-13–/– mice displayed significantly decreased severity of arthritis (50% to 60%) as analyzed by clinical and histological scoring methods.Conclusions
MMP-13 deficiency acts to suppress the local inflammatory responses. Therefore, MMP-13 has a role in the pathogenesis of arthritis, suggesting MMP-13 is a potential therapeutic target. 相似文献6.
Moore J. Rajasekaran K. Cary J. W. Chlan C. 《International journal of peptide research and therapeutics》2019,25(3):1135-1145
International Journal of Peptide Research and Therapeutics - The synthetic, linear peptide, D4E1, demonstrates antimicrobial activity against a broad spectrum of organisms including the toxigenic... 相似文献
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Increasing death rates due to antibiotic resistance deteriorate the existing treatment measures. Antimicrobial peptides have turned into the emerging cure for multidrug resistance. However, the stability and functionality determine an antimicrobial peptide as a drug. Analyses of the homodimeric β-helical peptide, gramicidin have suggested the significant role of gramicidin-A, gramicidin-B, and gramicidin-C as antimicrobial compounds, but the structural basis for understanding the stability and functionality is insufficient to resolve multidrug resistance. To identify the best template among gramicidin types as a therapeutic product, we combined a detailed comparative static analysis and dynamic analysis along with conformational free energy and secondary structure prediction. We observed that the high intramolecular interactions and the geometrical features favored gramicidin-A among other types of gramicidin. Our analyses further revealed that the secondary structure of gramicidin-A showed β sheets with coils along the conformations without any disruption, thereby enhanced its membrane interactions in terms of binding free energy. In conclusion, gramicidin-A has definitely showed enhanced structural stability and functionality; this could be considered the best template for a potential therapeutic product. 相似文献
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Tong T Fan W Zhao H Jin S Fan F Blanck P Alomo I Rajasekaran B Liu Y Holbrook NJ Zhan Q 《Experimental cell research》2001,265(1):64-72
Indian hedgehog (Ihh) is highly expressed in prehypertrophic chondrocytes in vivo and has been proposed to regulate the proliferation and maturation of chondrocytes and bone collar formation in the growth plate. In high-density cultures of rabbit growth-plate chondrocytes, Ihh mRNA was also expressed at the highest level in the prehypertrophic stage. To explore endogenous factors that regulate Ihh expression in chondrocytes, we examined the effects of various growth factors on Ihh mRNA expression in this system. Retinoic acid (RA) and bone morphogenetic protein-2 enhanced Ihh mRNA expression, whereas PTH/PTH-related peptide (PTHrP) markedly suppressed Ihh expression. RA at more than 10(-8) M induced the expression of Ihh and Patched 1 (Ptc1) within 3 h, before it increased the type X collagen mRNA level at 6-24 h. Cycloheximide blocked the up-regulation of Ihh by RA, indicating the requirement of de novo protein synthesis for this stimulation. These findings suggest that RA is involved in the up-regulation of Ihh during endochondral bone formation. In contrast to RA, PTH (1-84) at 10(-7) M abolished the mRNA expression of Ihh and Ptc1 within 2-4 h, before it suppressed the expression of type X collagen at 12-24 h. The inhibition of Ihh expression by PTH (1-84) did not require de novo protein synthesis. PTH (1-34), PTHrP (1-34), and (Bu)(2)cAMP also suppressed Ihh expression. On the other hand, Ihh has been reported to induce PTHrP synthesis in the perichondrium. Consequently, the direct inhibitory action of PTH/PTHrP on Ihh appears to be a negative feedback mechanism that prevents excess PTHrP accumulation in cartilage. 相似文献
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Jin YP Singh RP Du ZY Rajasekaran AK Rozengurt E Reed EF 《Journal of immunology (Baltimore, Md. : 1950)》2002,168(11):5415-5423
The development of chronic rejection is the major limitation to long-term allograft survival. HLA class I Ags have been implicated to play a role in this process because ligation of class I molecules by anti-HLA Abs stimulates smooth muscle cell and endothelial cell proliferation. In this study, we show that ligation of HLA class I molecules on the surface of human aortic endothelial cells stimulates phosphorylation of Src, focal adhesion kinase, and paxillin. Signaling through class I stimulated Src phosphorylation and mediated fibroblast growth factor receptor (FGFR) translocation to the nucleus. In contrast, Src kinase activity was not involved in class I-mediated transfer of FGFR from cytoplasmic stores to the cell surface. Inhibition of Src protein kinase activity blocked HLA class I-stimulated tyrosine phosphorylation of paxillin and focal adhesion kinase. Furthermore, HLA class I-mediated phosphorylation of the focal adhesion proteins and FGFR expression was inhibited by cytochalasin D and latrunculin A, suggesting a role for the actin cytoskeleton in the signaling process. These findings indicate that anti-HLA Abs have the capacity to transduce activation signals in endothelial cells that may promote the development of chronic rejection. 相似文献