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981.
Joshua W. Mugford Joshua Starmer Rex L. Williams Jr. J. Mauro Calabrese Piotr Mieczkowski Della Yee Terry Magnuson 《Genetics》2014,197(2):715-723
X chromosome inactivation (XCI) is an epigenetic process that almost completely inactivates one of two X chromosomes in somatic cells of mammalian females. A few genes are known to escape XCI and the mechanism for this escape remains unclear. Here, using mouse trophoblast stem (TS) cells, we address whether particular chromosomal interactions facilitate escape from imprinted XCI. We demonstrate that promoters of genes escaping XCI do not congregate to any particular region of the genome in TS cells. Further, the escape status of a gene was uncorrelated with the types of genomic features and gene activity located in contacted regions. Our results suggest that genes escaping imprinted XCI do so by using the same regulatory sequences as their expressed alleles on the active X chromosome. We suggest a model where regulatory control of escape from imprinted XCI is mediated by genomic elements located in close linear proximity to escaping genes. 相似文献
982.
983.
Joël Janin 《Protein science : a publication of the Protein Society》2014,23(12):1813-1817
A minimal model of protein–protein binding affinity that takes into account only two structural features of the complex, the size of its interface, and the amplitude of the conformation change between the free and bound subunits, is tested on the 144 complexes of a structure‐affinity benchmark. It yields Kd values that are within two orders of magnitude of the experiment for 67% of the complexes, within three orders for 88%, and fails on 12%, which display either large conformation changes, or a very high or a low affinity. The minimal model lacks the specificity and accuracy needed to make useful affinity predictions, but it should help in assessing the added value of parameters used by more elaborate models, and set a baseline for evaluating their performances. 相似文献
984.
Gramicidin A (gA) is a polypeptide antibiotic, which forms dimeric channels specific for monovalent cations in artificial and biological membranes. It is a polymorphic molecule that adopts a unique variety of helical conformations, including antiparallel double‐stranded ↑↓β5.6 or ↑↓β7.2 helices (number of residues per turn) and a single‐stranded β6.3 helix (the ‘channel form’). The behavior of gA‐Cs+ complex in the micelles of TX‐100 was studied in this work. Transfer of the complex into the micelles activates a cascade of sequential conformational transitions monitored by CD and FT‐IR spectroscopy: At the first step after Cs+ removal, the RH ↑↓β5.6 helix is formed, which has been discussed so far only hypothetically. Kinetics of the transitions was measured, and the activation parameters were determined. The activation energies of the ↑↓β5.6 → β‐helical monomer transition in dioxane and dioxane/water solutions were also measured for comparison. The presence of water raises the transition rate constant ~103 times but does not lead to crucial fall of the activation energy. All activation energies were found in the 20–25 kcal/mol range, i.e. much lower than would be expected for unwinding of the double helix (when 28 H‐bonds are broken simultaneously). These results can be accounted for in the light of local unfolding (or ‘cracking’) model for large scale conformational transitions developed by the P. G.Wolynes team [Miyashita O, Onuchic JN, Wolynes PG. Proc. Natl. Acad. Sci. USA 2003; 100: 12570‐12575.]. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
985.
986.
Hypericum attenuatum Choisy is a traditional Chinese herbal plant with multiple therapeutic effects. In this study, bioactivity-guided fractionation of Hypericum attenuatum Choisy extracts afforded three major flavonoids (including astragalin, guaijaverin and quercetin), which possessed α-Glucosidase inhibitory activity with IC50 values of 33.90±0.68 μM, 17.23±0.75 μM and 31.90±0.34 μM, respectively. Circular dichroism analysis revealed that all the three compounds could interact with α-glucosidase by inducing conformational changes of the enzyme. Molecular docking results indicated that they could bind to the active site in α-glucosidase, and the binding force was driven mainly by hydrogen bond. Additionally, isobolographic analysis of the interactions between two compounds showed that all the combinations presented a synergistic α-glucosidase inhibitory effect at lower concentrations, and the combination between quercetin and guaijaverin or astragalin exhibited the best synergistic effect. This research might provide a theoretical basis for the application of Hypericum attenuatum Choisy in treating hyperglycemia. 相似文献
987.
Min Hyeok Kim Sangjae Seo Jay Il Jeong Bum Joon Kim Wing Kam Liu Byeong Soo Lim Jae Boong Choi Moon Ki Kim 《Protein science : a publication of the Protein Society》2013,22(5):605-613
An elastic network model (ENM), usually Cα coarse‐grained one, has been widely used to study protein dynamics as an alternative to classical molecular dynamics simulation. This simple approach dramatically saves the computational cost, but sometimes fails to describe a feasible conformational change due to unrealistically excessive spring connections. To overcome this limitation, we propose a mass‐weighted chemical elastic network model (MWCENM) in which the total mass of each residue is assumed to be concentrated on the representative alpha carbon atom and various stiffness values are precisely assigned according to the types of chemical interactions. We test MWCENM on several well‐known proteins of which both closed and open conformations are available as well as three α‐helix rich proteins. Their normal mode analysis reveals that MWCENM not only generates more plausible conformational changes, especially for closed forms of proteins, but also preserves protein secondary structures thus distinguishing MWCENM from traditional ENMs. In addition, MWCENM also reduces computational burden by using a more sparse stiffness matrix. 相似文献
988.
Igor A. Kaltashov Cedric E. Bobst Rinat R. Abzalimov 《Protein science : a publication of the Protein Society》2013,22(5):530-544
Mass spectrometry is now an indispensable tool in the armamentarium of molecular biophysics, where it is used for tasks ranging from protein sequencing and mapping of post‐translational modifications to studies of higher order structure, conformational dynamics, and interactions of proteins with small molecule ligands and other biopolymers. This mini‐review highlights several popular mass spectrometry‐based tools that are now commonly used for structural studies of proteins beyond their covalent structure with a particular emphasis on hydrogen exchange and direct electrospray ionization mass spectrometry. 相似文献
989.
Krishna Chaitanya Bodapati Rania Soudy Hashem Etayash Michael Stiles Kamaljit Kaur 《Bioorganic & medicinal chemistry》2013,21(13):3715-3722
Class IIa bacteriocins are potent antimicrobial peptides produced by lactic acid bacteria to destroy competing microorganisms. The N-terminal domain of these peptides consists of a conserved YGNGV sequence and a disulphide bond. The YGNGV motif is essential for activity, whereas, the two cysteines involved in the disulphide bond can be replaced with hydrophobic residues. The C-terminal region has variable sequences, and folds into a conserved amphipathic α-helical structure. To elucidate the structure–activity relationship in the N-terminal domain of these peptides, three analogues (1–3) of a class IIa bacteriocin, Leucocin A (LeuA), were designed and synthesized by replacing the N-terminal β-sheet residues of the native peptide with shorter β-turn motifs. Such replacement abolished the antibacterial activity in the analogues, however, analogue 1 was able to competitively inhibit the activity of native LeuA. Native LeuA (37-mer) was synthesized using native chemical ligation method in high yield. Solution conformation study using circular dichroism spectroscopy and molecular dynamics simulations suggested that the C-terminal region of analogue 1 adopts helical folding as found in LeuA, while the N-terminal region did not fold into β-sheet conformation. These structure–activity studies highlight the role of proper folding and complete sequence in the activity of class IIa bacteriocins. 相似文献
990.
The native structure of proteins corresponds to the global minimum of the free energy. The replica-exchange method (REM) has been recently used to search for the energy minimum in a wide protein conformation space. For large systems, however, applying REM can be costly because the number of replicas required for conformational sampling increases. We have developed a variant of REM called fragment REM, which is based on the existence of correlations between the local amino acid sequence and the local structure. Equilibrium distributions for two peptides were computed by conventional molecular dynamics, REM and the proposed REM simulations. We found that the modified REM successfully reduces the number of replicas needed for the simulation. 相似文献