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      A molecular dynamics study of lunasin

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          Abstract

          Lunasin, a 43 amino acid peptide, suppresses chemically induced transformations in mammalian cells and skin carcinogenesis in mice. This peptide has also been reported to exhibit very good bioavailability after its oral administration. However, despite its biological and medicinal significance, the exact three-dimensional (3D) structure of lunasinis thus far not yet fully characterized. Thus this work is aimed at exploring the conformational profile of lunasin,using classical molecular dynamics (MD) simulations at the time scale of 300 ns. The results obtained from the MD trajectory reveal that lunasin has a strong propensity to exhibit three characteristic a helical bundles in its structure supported by residues His5-Cys10, Cys22-Ile30 and Asp35-Asp41. The reported cell adhesion motif (Arg-Gly-Asp) of lunasin responsible for its binding to cell chromatin, on other hand, did not exhibit any characteristic secondary feature. The structural information obtained from the current study could be useful to better understand the bioactive conformation of lunasin.

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          Most cited references 31

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          Dependence of paclitaxel sensitivity on a functional spindle assembly checkpoint.

          Paclitaxel stabilizes microtubules, causing mitotic arrest and activating the spindle assembly checkpoint. We determined whether suppression of the checkpoint genes Mad2 and BubR1 affects paclitaxel resistance and whether overexpression of Mad2 protein in checkpoint-defective cells enhances paclitaxel sensitivity. Suppression of Mad2 and BubR1 in paclitaxel-treated cancer cells abolished checkpoint function, resulting in paclitaxel resistance that correlated with suppression of cyclin-dependent kinase-1 activity. In contrast, overexpression of Mad2 in cells with a checkpoint defect attributable to low Mad2 expression restored checkpoint function, resulting in enhanced paclitaxel sensitivity that correlated with enhanced cyclin-dependent kinase-1 activity. However, overexpression of Mad2 failed to enhance paclitaxel sensitivity via checkpoint activation in Mad2-independent checkpoint-defective and -intact cells. Thus, checkpoint function is required for paclitaxel sensitivity. These findings show that any molecules that could interfere with the spindle assembly checkpoint could generate paclitaxel resistance in any patient.
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            Extracellular ATP in plants. Visualization, localization, and analysis of physiological significance in growth and signaling.

            Extracellular ATP (eATP) in animals is well documented and known to play an important role in cellular signaling (e.g. at the nerve synapse). The existence of eATP has been postulated in plants; however, there is no definitive experimental evidence for its presence or an explanation as to how such a polar molecule could exit the plant cell and what physiological role it may play in plant growth and development. The presence of eATP in plants (Medicago truncatula) was detected by constructing a novel reporter; i.e. fusing a cellulose-binding domain peptide to the ATP-requiring enzyme luciferase. Application of this reporter to plant roots allowed visualization of eATP in the presence of the substrate luciferin. Luciferase activity could be detected in the interstitial spaces between plant epidermal cells and predominantly at the regions of actively growing cells. The levels of eATP were closely correlated with regions of active growth and cell expansion. Pharmacological compounds known to alter cytoplasmic calcium levels revealed that ATP release is a calcium-dependent process and may occur through vesicular fusion, an important step in the polar growth of actively growing root hairs. Reactive oxygen species (ROS) activity at the root hair tip is not only essential for root hair growth, but also dependent on the cytoplasmic calcium levels. Whereas application of exogenous ATP and a chitin mixture increased ROS activity in root hairs, no changes were observed in response to adenosine, AMP, ADP, and nonhydrolyzable ATP (betagammameATP). However, application of exogenous potato (Solanum tuberosum) apyrase (ATPase) decreased ROS activity, suggesting that cytoplasmic calcium gradients and ROS activity are closely associated with eATP release.
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              Conformational preferences and pK(a) value of selenocysteine residue.

              The conformational preferences of the L-selenocysteine (Sec) dipeptides with selenol and selenolate groups (Ac-Sec-NHMe and Ac-Sec(-) -NHMe, respectively) and the apparent (i.e., macroscopic) pK(a) value of the Sec residue have been studied using the dispersion-corrected density functionals M06-2X and B2PLYP-D with the implicit solvation method in the gas phase and in water. In the gas phase, the backbone-to-backbone and/or side chain-to-backbone hydrogen bonds are found to contribute in stabilizing the most preferred conformations for the Sec and Sec(-) residues, as seen for the Cys and Cys(-) residues. However, the polyproline II-like conformations prevail over the conformations with the backbone-to-backbone hydrogen bonds in water because of the weakened hydrogen bonds by the favorable direct interactions between the backbone CO and HN groups and water molecules. The Sec and Sec(-) residues are found to adopt more various conformations than the Cys and Cys(-) residues in water, although the most preferred conformations of the neutral and/or anionic forms of the two residues are similar each other in the gas phase and in water. Using the statistically weighted free energies of the Sec and Sec(-) dipeptides in the gas phase and their solvation free energies, the pK(a) value of the Sec residue is estimated to be 5.47 at 25°C, which is in good agreement with the experimental value of 5.43 ± 0.02. It is found that the lower pK(a) value of the selenol side chain for the Sec residue by ∼3 units than the thiol side chain for the Cys residue is ascribed to the higher gas-phase acidity of the Sec residue.
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                Author and article information

                Affiliations
                [1 ] Durban University of Technology South Africa
                Contributors
                Role: ND
                Role: ND
                Journal
                sajc
                South African Journal of Chemistry
                S.Afr.j.chem. (Online)
                The South African Chemical Institute (Durban )
                1996-840X
                2012
                : 65
                : 0
                : 115-124
                S0379-43502012000100020

                http://creativecommons.org/licenses/by/4.0/

                Product
                Product Information: SciELO South Africa
                Categories
                Chemistry, Analytical
                Chemistry, Applied
                Chemistry, Inorganic & Nuclear
                Chemistry, Medicinal
                Chemistry, Multidisciplinary
                Chemistry, Organic
                Chemistry, Physical
                Electrochemistry

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