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排序方式: 共有203条查询结果,搜索用时 15 毫秒
91.
A proteomic analysis of human hemodialysis fluid 总被引:2,自引:0,他引:2
92.
Fibroblast growth factors (FGFs) play crucial roles in the regulation of key cellular processes such as angiogenesis, differentiation, and tumor growth. Suramin, a polysulfonated naphthylurea, is known to be a potent inhibitor of FGF-induced angiogenesis. Using isothermal titration calorimetry, we demonstrate that human acidic fibroblast growth factor (hFGF-1) binds to suramin with high affinity in the nanomolar range. The suramin:hFGF-1 binding stoichiometry is estimated to be 2:1. Size-exclusion chromatography data reveal that suramin oligomerizes hFGF-1 to form a stable tetramer. Thermal unfolding experiments monitored by steady state fluorescence, and limited trypsin digestion analysis data suggest that suramin-induced oligomerization of hFGF-1 occurs in two steps. The first step involves the binding of suramin at specific sites on the protein. Two molecules of suramin appear to bind simultaneously to one molecule of hFGF-1. Binding of suramin possibly involves formation of solvent-exposed nonpolar surfaces in hFGF-1. In the second step, FGF appears to oligomerize through coalescence of the solvent-accessible nonpolar surfaces. Results of the NMR experiments reveal that suramin binds to residues in the heparin binding pocket as well as to residues involved in FGF receptor binding. On the basis of the results of this study, we propose a model to explain the molecular mechanism(s) underlying the antimitogenic activity of suramin. To our knowledge, this is the first study in which suramin interaction sites on FGF have been characterized. 相似文献
93.
Morrell A Jayaraman M Nagarajan M Fox BM Meckley MR Ioanoviciu A Pommier Y Antony S Hollingshead M Cushman M 《Bioorganic & medicinal chemistry letters》2006,16(16):4395-4399
The indenoisoquinolines are a novel class of non-camptothecin topoisomerase I (Top1) inhibitors whose mechanism of action involves trapping the covalent complex formed between DNA and Top1 during cellular processes. As an ongoing evaluation of the indenoisoquinolines for Top1 inhibition and anticancer activity, indenoisoquinoline analogs have been screened in the National Cancer Institute's hollow fiber assay (HFA). Some of the derivatives demonstrated significant activity at intraperitoneal and subcutaneous fiber placement sites, along with net cancer cell kill in one or more cell lines. 相似文献
94.
Shanmugaraj Sathya Selvaraj Sudhagar Murugan Vidhya Priya Rajaganapathy Bharathi Raja Velusamy Shanmuganathan Muthusamy S. Niranjali Devaraj Baddireddi Subhadra Lakshmi 《Chemico-biological interactions》2010,188(3):412-420
Plumbago zeylanica, a traditional Indian herb is being used for the therapy of rheumatism and has been approved for anti-tumor activity. However, the molecular mechanisms involved in the biological action are not very well understood. In this study, the anti-invasive activities of P. zeylanica methanolic extract (PME) and pure compound 3β-hydroxylup-20(29)-ene-27,28-dioic acid (PZP) isolated from it are investigated in vitro. PME and PZP were noted to have the ability to induce apoptosis as assessed by flow cytometry. Further, the molecular mechanism of apoptosis induced by PME and PZP was found by the loss of mitochondrial membrane potential with the down regulation of Bcl-2, increased expression of Bad, release of cytochrome c, activation of caspase-3 and cleavage of PARP leading to DNA fragmentation. Importantly, both PME and PZP were observed to suppress MDA-MB-231 cells adhesion to the fibronectin-coated substrate and also inhibited the wound healing migration and invasion of MDA-MB-231 cells through the reconstituted extracellular matrix. Gelatin zymography revealed that PME and PZP decreased the secretion of matrix metalloproteinases-2 (MMP-2) and metalloproteinases-9 (MMP-9). Interestingly both PME and PZP exerted an inhibitory effect on the protein levels of p-PI3K, p-Akt, p-JNK, p-ERK1/2, MMP-2, MMP-9, VEGF and HIF-1α that are consistent with the observed anti-metastatic effect. Collectively, these data provide the molecular basis of the anti-proliferative and anti-metastatic effects of PME and PZP. 相似文献
95.
Kadapakkam Nandabalan Sangeetha Sundaresan Sujatha Velusamy Shanmuganathan Muthusamy Singaravel Anand Nirmal Nithya Devadasan Velmurugan Arun Balakrishnan Baddireddi Subhadra Lakshmi 《Biochimica et Biophysica Acta (BBA)/General Subjects》2010
Background
The present study focuses on identifying and developing an anti-diabetic molecule from plant sources that would effectively combat insulin resistance through proper channeling of glucose metabolism involving glucose transport and storage.Methods
Insulin-stimulated glucose uptake formed the basis for isolation of a bioactive molecule through column chromatography followed by its characterization using NMR and mass spectroscopic analysis. Mechanism of glucose transport and storage was evaluated based on the expression profiling of signaling molecules involved in the process.Results
The study reports (i) the isolation of a bioactive compound 3β-taraxerol from the ethyl acetate extract (EAE) of the leaves of Mangifera indica (ii) the bioactive compound exhibited insulin-stimulated glucose uptake through translocation and activation of the glucose transporter (GLUT4) in an IRTK and PI3K dependent fashion. (iii) the fate of glucose following insulin-stimulated glucose uptake was ascertained through glycogen synthesis assay that involved the activation of PKB and suppression of GSK3β.General significance
This study demonstrates the dual activity of 3β-taraxerol and the ethyl acetate extract of Mangifera indica as a glucose transport activator and stimulator of glycogen synthesis. 3β-taraxerol can be validated as a potent candidate for managing the hyperglycemic state. 相似文献96.
97.
Joseph Abhilash Kalarickal Vijayan Dileep Muthusamy Palanimuthu Krishnan Geethanandan Chittalakkotu Sadasivan Madhathilkovilakath Haridas 《Journal of molecular modeling》2013,19(8):3271-3278
Spatholobus parviflorus seed lectin (SPL) is a heterotetrameric lectin, with two α and two β monomers. In the crystal structure of SPL α monomer, two residues at positions 240 and 241 are missing. This region was modeled based on the positional and sequence similarities. The role of metal ions in SPL structure was analyzed by 10 ns molecular dynamics simulation. MD simulations were performed in the presence and absence of metal ions to explain the loss of haemagglutinating property of the lectin due to demetallization. Demetallized structure was found to deviate drastically at the metal binding loop region. Affinity of different sugars like N-acetyl galactosamine (GalNAc), D-galactose and lactose towards the native and demetallized protein was calculated by molecular docking studies. It was found that the sugar binding site got severely distorted in demetallized lectin. Consequently, sugar binding ability of lectin might be decreasing in the demetallized condition. Isothermal titration calorimetric (ITC) analysis of the sugars in the presence of native and demetallized protein confirmed the in silico results. It was observed after molecular dynamics simulations, that significant structural deviations were not caused in the quaternary structure of demetallized lectin. It was confirmed that the structural changes modified the sugar binding ability, as well as sugar specificity of the present lectin. The role of metal ions in sugar binding is described based on the in silico studies and ITC analysis. A comprehensive analysis of the ITC data suggests that the sugar specificity of the metal bound lectin and the loss of sugar specificity due to metal chelation are not linear. Figure
Role of metal ions in sugar binding of Spatholobus parviflorus seed lectin 相似文献
98.
Muthusamy Karthikeyan Palani Kirubakaran Kh. Dhanachandra Singh Bhuvaneshwari Sampath Gopinath Krishnasamy 《Journal of biomolecular structure & dynamics》2013,31(5):816-830
The existing H1N1 (2009) swine flu is pandemic in nature and is responsible for global economic losses and fatalities. Among the eight gene segments of H1N1, hemagglutinin (HA) plays a major role in the attachment of the virus to the host cell surface and entry of viral RNA into the host cell leads to infection. In this study, sequence and phylogenetic analysis of the H1N1 (2009) HA, from Mexico City along with 1952 sequences, from different subtypes of pandemic influenza A virus were studied and results showed that the closest relationship of H1N1 (2009) Mexico strain was with the H1N1 (2007) Mallard Norway strain. Analysis of secondary structures predicted from the protein sequence revealed that diminishing of alpha helixes was observed in many areas of the sequences between the years 2005 to 2010. Conversely, analysis at the structural level is necessary to critically assess the functional significance. Structural level investigation was therefore done for the above said proteins by constructing the 3D structure of these proteins through homology modeling. The models were validated and structural level similarities were evaluated through superimposition. Subsequently, docking studies were done to find the binding mode of the sialic acid (SA) with influenza HA. Molecular dynamics simulations were executed to study the interactions of SA molecule with the HA. Energetic analysis reveals that van der Waal interaction is more favorable for binding of HA with SA of the whole influenza virus. Binding pocket analysis shows that intensities of H-bond donor and acceptor are more in H1N1 (2009). 相似文献
99.
This paper describes a protocol to develop cotton mutant lines with improved yield and fiber characters. Immature ovules [(15-day
post-anthesis ovules (dap)] were irradiated with 10–50 Gy gamma rays and treated with 1–5 mM EMS and SA to investigate the
stimulatory effects of mutagenic treatments. During the subsequent field trials, the mutant lines showed significant variations
from control lines. Lower dose/concentration of mutagenic treatments effectively stimulate the agronomical characters like
early flowering, plant height, number of bolls, yield of seed cotton, ginning percent, seed index, harvest index and fiber
characters while exposure at higher dose/concentration results in lowering the value of the parameters. Consequently, we use
this approach to induce genetic variability for obtaining novel mutant cotton cultivars. Among the 19 different mutant lines
isolated from the study, M7 showed higher morphological variations in terms of yield characters such as plant height, number
of bolls, yield of seed cotton, ginning percent and fiber characters. Significant increase in cellulose content was also noted
in mutant lines, whereas moderate increase was observed in total fiber units of the mutant lines. The selected cotton mutant
lines for cultivars were investigated systematically; these lines significantly increased the potential for agronomical enhancement
of cotton yield. 相似文献