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941.
Tao Luo Jinhyuk Lee Zhi-Rong Lü Hang Mu Li-Mei Yue Yong-Doo Park Zhuo-Ming Ye 《The protein journal》2016,35(3):218-224
α-Glucosidase is a critical metabolic enzyme that produces glucose molecules by catalyzing carbohydrates. The aim of this study is to elucidate biological toxicity of Cd2+ based on α-glucosidase activity and conformational changes. We studied Cd2+-mediated inactivation as well as conformational modulation of α-glucosidase by using kinetics coupled with simulation of molecular dynamics. The enzyme was significantly inactivated by Cd2+ in a reversibly binding behavior, and Cd2+ binding induced a non-competitive type of inhibition reaction (the K i was calculated as 0.3863 ± 0.033 mM). Cd2+ also modulated regional denaturation of the active site pocket as well as overall partial tertiary structural change. In computational simulations using molecular dynamics, simulated introduction of Cd2+ induced in a depletion of secondary structure by docking Cd2+ near the saccharides degradation at the active site, suggesting that Cd2+ modulating enzyme denaturation. The present study elucidated that the binding of Cd2+ triggers conformational changes of α-glucosidase as well as inactivates catalytic function, and thus suggests an explanation of the deleterious effects of Cd2+ on α-glucosidase. 相似文献
942.
Soumyabrata Banerjee Mrinal K. Poddar 《International journal of peptide research and therapeutics》2016,22(4):471-480
It is well known that the monoamine oxidase (MAO) activity deregulates during aging along with anti-oxidant activity. Carnosine (β-Ala-l-His) is an endogenous dipeptide biomolecule, having both anti-oxidant and anti-glycating properties. The present study deals with the effect of carnosine on aging-induced changes in MAO-A mRNA expression of brain regions and blood platelets in relation to their MAO-A activity. Results showed that aging significantly and characteristically increased the brain regional MAO-A mRNA whereas, in blood platelets it was significantly reduced with an increase in blood platelet counts. Carnosine attenuated both aging-induced (i) increase in brain regional MAO-A mRNA expression and blood platelet count, (ii) decrease in blood platelet MAO-A mRNA expression and its (platelet MAO-A) activity without affecting the young rats’ brain regions and platelet. The present results thus suggest that carnosine attenuated and restored the aging-induced (a) increase of platelet count and (b) changes in brain regional and blood platelet MAO-A mRNA expression and (c) decrease in platelet MAO-A activity, towards their respective basal level that were observed in young rats. 相似文献
943.
Xiaole Chen He Wang Lei Wang Mei Zhou Tianbao Chen Chris Shaw 《The protein journal》2016,35(4):291-299
The chemical compounds synthesised and secreted from the dermal glands of amphibian have diverse bioactivities that play key roles in the hosts’ innate immune system and in causing diverse pharmacological effects in predators that may ingest the defensive skin secretions. As new biotechnological methods have developed, increasing numbers of novel peptides with novel activities have been discovered from this source of natural compounds. In this study, a number of defensive skin secretion peptide sequences were obtained from the European edible frog, P. kl. esculentus, using a ‘shotgun’ cloning technique developed previously within our laboratory. Some of these sequences have been previously reported but had either obtained from other species or were isolated using different methods. Two new skin peptides are described here for the first time. Esculentin-2c and Brevinin-2Tbe belong to the Esculentin-2 and Brevinin-2 families, respectively, and both are very similar to their respective analogues but with a few amino acid differences. Further, [Asn-3, Lys-6, Phe-13] 3-14-bombesin isolated previously from the skin of the marsh frog, Rana ridibunda, was identified here in the skin of P. kl. esculentus. Studies such as this can provide a rapid elucidation of peptide and corresponding DNA sequences from unstudied species of frogs and can rapidly provide a basis for related scientific studies such as those involved in systematic or the evolution of a large diverse gene family and usage by biomedical researchers as a source of potential novel drug leads or pharmacological agents. 相似文献
944.
Natan Roberto de Barros Matheus Carlos Romeiro Miranda Felipe Azevedo Borges Ricardo José de Mendonça Eduardo Maffud Cilli Rondinelli Donizetti Herculano 《International journal of peptide research and therapeutics》2016,22(4):435-444
The demand for biomaterials with properties that provide sustained release of substances with pharmacological interest is constant. One candidate for applications in this area is the Natural Rubber Latex (NRL) extracted from the rubber tree Hevea brasiliensis. Recent studies indicate the NRL as a matrix for sustained release, showing promising results for biomedical applications such as: can stimulate natural angiogenesis and is capable of adhering cells on its surface, promoting the replacement and regeneration of tissue. So, the NRL is an excellent candidate to propitiate the sustained release of peptides of pharmacological interest such as oxytocin, a hormonal peptide which has the function to promote uterine muscle contractions and reduce bleeding during childbirth, and stimulate the release of breast milk. Results demonstrated that 90 μg mL?1 (45 %) of the incorporated peptide in Natural Rubber Latex Biomedical (NRLb) functionalized membranes was released at 10 h in phosphate-buffered saline (PBS) solution. Swelling kinetics assay showed that the NRLb membranes are able to absorb over a period of 16 h up to 1.08 grams of water per grams of membrane. Scanning electron microscopy showed that the peptide was adsorbed on the surface and within NRLb membrane. Fourier transform infrared and Derivative Thermogravimetric analysis indicated that oxytocin did not interacted chemically with the membrane. Furthermore, hemolysis of erythrocytes, quantified spectrophotometrically using materials (Oxytocin, NRLb, and NRLb + Oxytocin) showed no hemolytic effects up to 100 μg mL?1 (compounds and mixtures), indicating no detectable disturbance of the red blood cell membranes. Based on these results it was possible to conclude that the NRLb has shown effectiveness as a model in the release of peptides with pharmacological interest. 相似文献
945.
946.
Lakshmi A. Dave Maria Hayes Paul J. Moughan Shane M. Rutherfurd 《International journal of peptide research and therapeutics》2016,22(3):355-369
Human gastrointestinal endogenous proteins (GEP) include the proteins mucins, serum albumin, digestive enzymes, and proteins from sloughed epithelial and microbial-cells. GEP play a vital role in the digestion of food, but are also simultaneously digested by proteases and peptidases of the gastrointestinal tract (GIT). Recent studies suggest that during gastrointestinal digestion, similar to dietary proteins, GEP may also give rise to bioactive peptides. In the present study, the protein sequences of 11 representative GEP were subjected to simulated in silico GIT (SIGIT) digestion. Following SIGIT digestion, 19 novel GEP-derived peptide sequences were selected using quantitative structure activity relationship rules for chemical synthesis. The peptides were then tested for their in vitro dipeptidyl peptidase IV (DPP-IV) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) inhibition, and for their ferric reducing antioxidant power (FRAP). Two novel DPP-IV inhibitory peptides with the amino acid sequences RPCF (IC50 = 800.51 ± 49.00 µM) and MIM (IC50 = 1056.78 ± 61.11 µM), and five novel antioxidant peptides CCK, RPCF, CRPK, QQCP and DCR were identified. The results of this study indicate that GEP are a significant source of bioactive peptides with potential novel bioactive peptide fragments within their sequences. 相似文献
947.
Chitobiase (CHB) is an important enzyme for the production of N-acetyl-d-glucosamine from the chitin biopolymer in the series of chitinolytic enzymes. Majority of over-expressed CHB (58 %) in E. coli expression system led to formation of inclusion bodies. The production and soluble yield of active CHB was enhanced by co-expression with GroEL/ES chaperonin, optimizing culture conditions and solubilization followed by refolding of remaining inactive chitobiase present in the form of inclusion bodies. The growth of recombinant E. coli produced 42 % CHB in soluble form and the rest (~58 %) as inclusion bodies. The percentage of active CHB was enhanced to 71 % by co-expression with GroEL/ES chaperonin system and optimizing culture conditions (37 °C, 200 rpm, IPTG—0.5 mM, l-arabinose—13.2 mM). Of the remaining inactive CHB present in inclusion bodies, 37 % could be recovered in active form using pulsatile dilution method involving denaturants (2 M urea, pH 12.5) and protein refolding studies (1.0 M l-arginine, 5 % glycerol). Using combinatorial approach, 80 % of the total CHB expressed, could be recovered from cells grown in one litre of LB medium is a step forward in replacing hazardous chemical technology by biotechnological process for the production of NAG from chitinous waste. 相似文献
948.
949.
Arezou Ghahghaei Sima Shahraki 《International journal of peptide research and therapeutics》2016,22(1):23-29
Alzheimer’s disease is associated with the fibril formation of β-amyloid peptide in extracellular plaque. β-Casein is a milk protein that has shown a remarkable ability to stabilize proteins by inhibiting their protein aggregation and precipitation. The aim of this study was to test in vitro the ability of β-casein to bind the Aβ1–40, change the structure and inhibit the formation of amyloid fibrils in Aβ1–40. Results from the ThT binding assay indicated that incubation of Aβ1–40 with β-casein retarded amyloid fibril formation of Aβ1–40 in a concentration dependent manner such that at a ratio of 1:1 (w:w) led to a significant reduction in the amount of fluorescent intensity. The results from transmission electron microscopy (TEM) also showed that β-casein significantly reduced the number and size of the Aβ1–40 fibrils, suggesting that the chaperone bound to the Aβ1–40 fibrils and/or interacted with the fibrils in some way. ANS results also showed that β-casein significantly decreased the exposed hydrophobic surface in Aβ1–40. Following an ANS binding assay, CD spectroscopy results also showed that incubation of Aβ1–40 resulted in a structural transition to a β-sheet. In the presence of β-casein, however, α-helical conformation was observed which indicated stabilization of the protein. These results reveal the highly efficacious chaperone action of β-casein against amyloid fibril formation of Aβ1–40. These results suggest that in vitro, β-casein binds to the Aβ1–40 fibrils, alters the Aβ1–40 structure and prevents amyloid fibril formation. This approach may result in the identification of a chaperone mechanism for the treatment of neurological diseases. 相似文献
950.
Shaminea Sritharan Thirumulu Ponnuraj Kannan Mohd Nor Norazmi Asma Abdullah Nurul 《International journal of peptide research and therapeutics》2016,22(4):517-526
Cytokines such as interleukin-6 (IL-6) and IL-17 which act as key regulators of the immune response have been identified to have a potential role in the bone remodeling mechanism. Receptor activator of NF-κB ligand (RANKL) has been shown to regulate osteoclast differentiation and function while the osteoprotegerin (OPG) blocks the binding of RANKL and inhibits the differentiation of osteoclasts, thus favoring osteogenesis. Alkaline phosphatase (ALP) on the other hand works as early mineralization indicator in bone regulation. The current study aims to determine the potential role of IL-6 and IL-17A in regulating the OPG/RANKL system of the murine osteoblast cell line (MC3T3-E1). Gene expression analysis showed significant up-regulation of OPG and ALP by all the treated groups (rIL-6, rIL-17A and rIL-6 + rIL-17A). In contrast, treatment of cells with rIL-6 and/or rIL-17A showed down-regulation of RANKL expression. Interestingly, the osteoblast cells treated with combinations of rIL-6 + rIL17A showed marked increased in OPG/RANKL ratio. Similar pattern of protein expression was observed in the osteoblasts treated with rIL-6 and/or rIL-17A as detected by western blotting and ELISA. These findings suggest a new mechanism of regulation by these cytokines on the expression of OPG and RANKL, which could promote osteogenesis and diminish osteoclastogenesis. 相似文献