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141.
Sameer Shakeel Ansari Rizwan Hasan Khan 《Journal of biomolecular structure & dynamics》2013,31(13):3362-3375
Intermolecular interaction study of human serum albumin (HSA) with two anthraquinones i.e. danthron and quinizarin has been performed through fluorescence, UV-vis and CD spectroscopy along with docking analysis. The titration of drugs into HSA solution brought about the quenching of fluorescence emission by way of complex formation. The binding constants were found to be 1.51 × 104 L mol?1 and 1.70 × 104 L mol?1 at λexc = 280 nm while at λexc = 295 nm, the values of binding constants were 1.81 × 104 L mol?1 and 1.90 × 104 L mol?1 which hinted toward binding of both the drugs in the vicinity of subdomain IIA. Different temperature study revealed the presence of static quenching mechanism. Moreover, more effective quenching of the fluorescence emission was observed at λexc = 295 nm which also suggested that both the drug molecule bind nearer to Trp-214. Thermodynamic parameters showed that hydrophobic interaction was the major force behind the binding of drugs. The UV-vis spectroscopy testified the formation of complex in both the systems and primary quenching mechanism as static one. The changes in secondary structure and α-helicity in both the systems were observed by circular dichroism spectroscopy. Furthermore, molecular docking analysis predicted the probable binding site of drugs in subdomain IIA of HSA molecule. The types of amino acid residues surrounding the drug molecule advocated that van der Waals forces, hydrophobic forces and electrostatic forces played a vital role in the stabilization of drug-protein complex formed. 相似文献
142.
Mahboobeh Zolfagharzadeh Ahmad Asoodeh Mohammad Reza Saberi 《Journal of biomolecular structure & dynamics》2013,31(12):1936-1952
This paper describes the interaction between 2,4-dinitrophenol (DNP) with the two drug carrier proteins – human serum albumin (HSA) and human holo transferrin (HTF). Hence, binding characteristics of DNP to HSA and HTF were analyzed by spectroscopic and molecular modeling techniques. Based on results obtained from fluorescence spectroscopy, DNP had a strong ability to quench the intrinsic fluorescence of HSA and HTF through a static quenching procedure. The binding constant and the number of binding sites were calculated as 2.3?×?1011?M?1 and .98 for HSA, and 1.7?×?1011?M?1 and 1.06 for HTF, respectively. In addition, synchronous fluorescence results showed that the microenvironment of Trp had a slight tendency of increasing its hydrophobicity, whereas the microenvironment of the Tyr residues of HSA did not change and that of HTF showed a significant trend (red shift of about 4?nm) of an increase in polarity. The distance between donor and acceptor was obtained by the Förster energy according to fluorescence resonance energy transfer, and was found to be 3.99 and 3.72?nm for HSA and HTF, respectively. The critical induced aggregation concentration (CCIAC) of the drug on both proteins was determined and confirmed by an inflection point of the zeta potential behavior. Circular dichroism data revealed that the presence of DNP caused a decrease of the α-helical content of HSA and HTF, and induced a remarkable mild denaturation of both proteins. The molecular modeling data confirmed our experimental results. This study is deemed useful for determining drug dosage. 相似文献
143.
L.-S. Kan D. E. Callahan T. L. Trapane P. S. Miller P. O.P. Ts'o D. H. Huang 《Journal of biomolecular structure & dynamics》2013,31(5):911-933
Abstract Triplex and duplex formation of two deoxyribohexadecamers d-A-(G-A)7-G (a) and d-C-(T-C)7-T (b) have been studied by UV, CD, fluorescence, and proton NMR spectroscopy. Optical studies of a and b at dilute concentrations (μM range) yielded results similar to those seen for polymers of the same sequence, indicating that these hexadecamers have properties similar to the polymers in regard to triplex formation. The CD spectra of concentrated NMR samples (mM range) are similar to those observed at optical concentrations at both low and high pH, making possible a correlation between CD and NMR studies. In NMR spectra, two imido NH-N hydrogen bonded resonance envelopes at 12.6 and 13.7 ppm indicate that only the duplex conformation is present at pH > 7.7. Four new NH-N hydrogen-bonded resonance envelopes at 12.7, 13.5, 14.2. and 14.9 ppm are observed under acidic conditions (pH 5.6) and the two original NH-N resonances gradually disappear as the pH is lowered. Assignment of these four peaks to Watson-Crick G · C, Hoogsteen T · A. Watson-Crick A · T. and Hoogsteen C+ · G hydrogen-bonded imidos, respectively, confirm the formation of triple-stranded DNA NMR results also show that triplex is more stable than duplex at the same salt condition and that triplex melts to single strands directly without going through a duplex intermediate. However, in the melting studies, a structural change within the triple-stranded complex is evident at temperatures significantly below the major helix-to-coil transition. These studies demonstrate the feasibility of using NMR spectroscopy and oligonucleotide model compounds a and b for the study of DNA triplex formation. 相似文献
144.
Anil K. Mantha Indu R. Chandrashekar Najma Z. Baquer Sudha M. Cowsik 《Journal of biomolecular structure & dynamics》2013,31(2):137-147
Abstract Neurokinin B (NKB), a decapeptide of mammalian origin exhibits a variety of biological activities such as regulatory functions in reproduction, pre-eclampsia and neuroprotection in Alzheimer's disease. In order to gain insight into structure-function relationship, three- dimensional structure of NKB has been investigated using CD spectropolarimetry and two-dimensional proton nuclear magnetic resonance (2D 1H-NMR) spectroscopy in aqueous and membrane mimetic solvents. Unambiguous NMR assignments of resonances have been made with the aid of correlation spectroscopy (DQF-COSY and TOCSY) experiments and Nuclear Overhauser Effect Spectroscopy (NOESY) experiments. Distance constraints obtained from the NMR data have been used to generate a family of structures, which have been refined using restrained energy minimization and dynamics. Our data show that a helical structure is induced in NKB, in presence of perdeuterated dodecyl phosphocholine (DPC) micelles, a membrane model system. Further, the conformation adopted by NKB in presence of DPC micelles represents a structural motif typical of neurokinin-3 selective agonists. 相似文献
145.
C. N. N′ soukpoé-Kossi C. St-Louis M. Beauregard M. Subirade R. Carpentier S. Hotchandani 《Journal of biomolecular structure & dynamics》2013,31(3):277-283
Abstract Resveratrol (Res), a polyphenolic compound found largely in the skin of red grape and wine, exhibits a wide range of pharmaceutical properties and plays a role in prevention of human cardiovascular diseases [Pendurthi et al., Arterioscler. Thromb. Vasc. Biol. 19, 419–426 (1999)]. It shows a strong affinity towards protein binding and used as inhibitor for cyclo- oxygenase and ribonuclease reductase. The aim of this study was to examine the interaction of resveratrol with human serum albumin (HSA) in aqueous solution at physiological conditions, using a constant protein concentration (0.3 mM) and various pigment contents μM to mM). FTIR, UV-Visible, CD, and fluorescence spectroscopic methods were used to determine the resveratrol binding mode, the binding constant and the effects of pigment complexation on protein secondary structure. Structural analysis showed that resveratrol bind non-specifically (H-bonding) via polypeptide polar groups with overall binding constant of KRes = 2.56× 105 M?1. The protein secondary structure, analysed by CD spectroscopy, showed no major alterations at low resveratrol concentrations (0.125 mM), whereas at high pigment content (1 mM), major increase of α-helix from 57% (free HSA) to 62% and a decrease of β-sheet from 10% (free HSA) to 7% occurred in the resveratrol-HSA complexes. The results indicate a partial stabilization of protein secondary structure at high resveratrol content. 相似文献
146.
Ana C. Santos Joana Cunha F. Veiga A. Cordeiro-da-Silva Antonio J. Ribeiro 《Carbohydrate polymers》2013
Alginate-dextran sulfate (ADS) microgel has been used to protect insulin from gastrointestinal attack and as a carrier to promote insulin permeation through intestinal epithelium. The throughput of ADS submicron particles generation by emulsification/internal gelation is limited by its wide size distribution. 相似文献
147.
G. Daniel Grass Lauren B. Tolliver Momka Bratoeva Bryan P. Toole 《The Journal of biological chemistry》2013,288(36):26089-26104
The immunoglobulin superfamily glycoprotein CD147 (emmprin; basigin) is associated with an invasive phenotype in various types of cancers, including malignant breast cancer. We showed recently that up-regulation of CD147 in non-transformed, non-invasive breast epithelial cells is sufficient to induce an invasive phenotype characterized by membrane type-1 matrix metalloproteinase (MT1-MMP)-dependent invadopodia activity (Grass, G. D., Bratoeva, M., and Toole, B. P. (2012) Regulation of invadopodia formation and activity by CD147. J. Cell Sci. 125, 777–788). Here we found that CD147 induces breast epithelial cell invasiveness by promoting epidermal growth factor receptor (EGFR)-Ras-ERK signaling in a manner dependent on hyaluronan-CD44 interaction. Furthermore, CD147 promotes assembly of signaling complexes containing CD147, CD44, and EGFR in lipid raftlike domains. We also found that oncogenic Ras regulates CD147 expression, hyaluronan synthesis, and formation of CD147-CD44-EGFR complexes, thus forming a positive feedback loop that may amplify invasiveness. Last, we showed that malignant breast cancer cells are heterogeneous in their expression of surface-associated CD147 and that high levels of membrane CD147 correlate with cell surface EGFR and CD44 levels, activated EGFR and ERK1, and activated invadopodia. Future studies should evaluate CD147 as a potential therapeutic target and disease stratification marker in breast cancer. 相似文献
148.
Manabu Takahashi Hiroaki Yagyu Fumiko Tazoe Shuichi Nagashima Taichi Ohshiro Kenta Okada Jun-ichi Osuga Ira J. Goldberg Shun Ishibashi 《Journal of lipid research》2013,54(4):1124-1134
The role of macrophage lipoprotein lipase (LpL) in the development of atherosclerosis and adiposity was examined in macrophage LpL knockout (MLpLKO) mice. MLpLKO mice were generated using cre-loxP gene targeting. Loss of LpL in macrophages did not alter plasma LpL activity or lipoprotein levels. Incubation of apolipoprotein E (ApoE)-deficient β-VLDL with peritoneal macrophages from ApoE knockout mice lacking macrophage LpL (MLpLKO/ApoEKO) led to less cholesteryl ester formation than that found with ApoEKO macrophages. MLpLKO/ApoEKO macrophages had reduced intracellular triglyceride levels, with decreased CD36 and carnitine palmitoyltransferase-1 mRNA levels compared with ApoEKO macrophages, when incubated with VLDL. Although both MLpLKO/ApoEKO and ApoEKO mice developed comparable hypercholesterolemia in response to feeding with a Western-type diet for 12 weeks, atherosclerosis was less in MLpLKO/ApoEKO mice. Epididymal fat mass and gene expression levels associated with inflammation did not differ between the two groups. In conclusion, macrophage LpL plays an important role in the development of atherosclerosis but not adiposity. 相似文献
149.
150.
Natalia A. Moroz Stefanie M. Novak Ricardo Azevedo Mert Colpan Vladimir N. Uversky Carol C. Gregorio Alla S. Kostyukova 《The Journal of biological chemistry》2013,288(7):4899-4907
Tropomodulin (Tmod) is an actin-capping protein that binds to the two tropomyosins (TM) at the pointed end of the actin filament to prevent further actin polymerization and depolymerization. Therefore, understanding the role of Tmod is very important when studying actin filament dependent processes such as muscle contraction and intracellular transport. The capping ability of Tmod is highly influenced by TM and is 1000-fold greater in the presence of TM. There are four Tmod isoforms (Tmod1–4), three of which, Tmod1, Tmod3, and Tmod4, are expressed in skeletal muscles. The affinity of Tmod1 to skeletal striated TM (stTM) is higher than that of Tmod3 and Tmod4 to stTM. In this study, we tested mutations in the TM-binding sites of Tmod1, using circular dichroism (CD) and prediction analysis (PONDR). The mutations R11K, D12N, and Q144K were chosen because they decreased the affinity of Tmod1 to stTM, making it similar to that of affinity of Tmod3 and Tmod4 to stTM. Significant reduction of inhibition of actin pointed-end polymerization in the presence of stTM was shown for Tmod1 (R11K/D12N/Q144K) as compared with WT Tmod1. When GFP-Tmod1 and mutants were expressed in primary chicken skeletal myocytes, decreased assembly of Tmod1 mutants was revealed. This indicates a direct correlation between TM-binding and the actin-capping abilities of Tmod. Our data confirmed the hypothesis that assembly of Tmod at the pointed-end of the actin filament depends on its TM-binding affinity. 相似文献