48 research outputs found

    Aniline-Hydroxylation Activity of a Flavin-linked βαβα-Type Polypeptide Packing an Iron Porphyrin

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    Polypeptide containing iron porphyrin and flavin showed aniline-hydroxylation activity in the presence of 1-benzyl-1,4-dihydronicotinamide and O2. The increased activity at pH 5.5 compared with that at pH 7.0 suggests that the dissociation of His from the iron porphyrin favored the hydroxylation

    Fluorescence Energy Transfer in Dendritic Poly(L-lysine)s Combining Thirty-two Free Base- and Zinc(II)-porphyrins in Scramble Fashion

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    Dendritic poly(L-lysine)s combining thirty-two free base- and Zn(II)-porphyrins in scramble fashion were successfully synthesized and exhibited highly efficient (85%) fluorescence energy transfer from Zn(II)-porphyrins to free base-porphyrins

    The Conformation of de Novo Designed Amphiphilic Peptides with Six or Nine L-2-(2,2,2-Trifluoroethyl)glycines as the Hydrophobic Amino Acid

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    Amphiphilic 21-peptides with six and nine L-2-(2,2,2-trifluoroethyl)glycines as the hydrophobic amino acids and lysine and glutamic acid as the hydrophilic amino acids were synthesized. The CD spectra showed that these peptides with L-2-(2,2,2-trifluoroethyl)glycines took a random conformation in H2O. On the contrary, similar amphiphilic 21-peptides with leucine as the hydrophobic amino acids took a helical conformation in H2O. The peptides with L-2-(2,2,2-trifluoroethyl)glycines took a helical conformation in H2O containing a > 20% volume of 2,2,2-trifluoroethanol. These facts suggested the hydrophobic nature of the L-trifluoroethylglycines. The peptide with six L-2-(2,2,2-trifluoroethyl)glycines took a helical structure in methanol, however it slowly changed into the β-structure within 24 h. Interestingly, the peptide with nine L-2-(2,2,2-trifluoroethyl)glycines formed a stable helix under the same conditions. The peptide with nine L-2-(2,2,2-trifluoroethyl)glycines preferred a helical structure, probably because the assembling of the Tfeg side chains was more effective in forming its helix rather than the β-structure

    The NMR Spectroscopic Evaluation of Immobility of a Crowd of Porphyrin Rings Combined with Dendritic Poly(L-lysine)s

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    Since the dendritic poly(L-lysine)s combining eight to thirty-two free base-porphyrins showed split circular dichroism at the Soret band in toluene/N,N-dimethylformamide (9/1, v/v), the immobility of porphyrin rings was evaluated by 1H NMR measurements in terms of the peak width at half-height and spin-lattice relaxation time

    Complexation of 4,4′-Dipyridyl Derivatives Changed the Orientations of Metalloporphyrins Linked to the Cyclic Peptide Gramicidin S

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    Pairs of Zn and Co(III) porphyrins linked to the natural cyclic β-sheet peptide, Gramicidin S, formed stable host-guest complexes with the 4,4′-dipyridyl derivatives in dichloromethane, in which the Cotton effects reflected the orientational changes of the metalloporphyrins upon the complexations

    CD Investigation of Porphyrin-Porphyrin Interaction with Links to Acyclic β-Sheet Peptide Self-Assembled in an Aqueous Media

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    Amphiphilic peptide, Ac-Cys(Por)-Lys-Val-(-Ser-Val-)n-Lys-Val-NH2 (n = 0 or 1, Cys(Por) = side-chain porphyrin-linked Cys), self-assembled to form the β-sheet in buffer solution-2,2,2-trifluoroethanol and showed exciton coupled Cotton effects in the porphyrin region due to the closely ori?ented porphyrin

    Histone H4 Lys 20 Monomethylation of the CENP-A Nucleosome Is Essential for Kinetochore Assembly

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    SummaryIn vertebrate cells, centromeres are specified epigenetically through the deposition of the centromere-specific histone CENP-A. Following CENP-A deposition, additional proteins are assembled on centromeric chromatin. However, it remains unknown whether additional epigenetic features of centromeric chromatin are required for kinetochore assembly. Here, we used ChIP-seq analysis to examine centromere-specific histone modifications at chicken centromeres, which lack highly repetitive sequences. We found that H4K20 monomethylation (H4K20me1) is enriched at centromeres. Immunofluorescence and biochemical analyses revealed that H4K20me1 is present at all centromeres in chicken and human cells. Based on immunoprecipitation data, H4K20me1 occurs primarily on the histone H4 that is assembled as part of the CENP-A nucleosome following deposition of CENP-A into centromeres. Targeting the H4K20me1-specific demethylase PHF8 to centromeres reduces the level of H4K20me1 at centromeres and results in kinetochore assembly defects. We conclude that H4K20me1 modification of CENP-A nucleosomes contributes to functional kinetochore assembly

    Histone Deacetylases Control Neurogenesis in Embryonic Brain by Inhibition of BMP2/4 Signaling

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    Background Histone-modifying enzymes are essential for a wide variety of cellular processes dependent upon changes in gene expression. Histone deacetylases (HDACs) lead to the compaction of chromatin and subsequent silencing of gene transcription, and they have recently been implicated in a diversity of functions and dysfunctions in the postnatal and adult brain including ocular dominance plasticity, memory consolidation, drug addiction, and depression. Here we investigate the role of HDACs in the generation of neurons and astrocytes in the embryonic brain. Principal Findings As a variety of HDACs are expressed in differentiating neural progenitor cells, we have taken a pharmacological approach to inhibit multiple family members. Inhibition of class I and II HDACs in developing mouse embryos with trichostatin A resulted in a dramatic reduction in neurogenesis in the ganglionic eminences and a modest increase in neurogenesis in the cortex. An identical effect was observed upon pharmacological inhibition of HDACs in in vitro-differentiating neural precursors derived from the same brain regions. A reduction in neurogenesis in ganglionic eminence-derived neural precursors was accompanied by an increase in the production of immature astrocytes. We show that HDACs control neurogenesis by inhibition of the bone morphogenetic protein BMP2/4 signaling pathway in radial glial cells. HDACs function at the transcriptional level by inhibiting and promoting, respectively, the expression of Bmp2 and Smad7, an intracellular inhibitor of BMP signaling. Inhibition of the BMP2/4 signaling pathway restored normal levels of neurogenesis and astrogliogenesis to both ganglionic eminence- and cortex-derived cultures in which HDACs were inhibited. Conclusions Our results demonstrate a transcriptionally-based regulation of BMP2/4 signaling by HDACs both in vivo and in vitro that is critical for neurogenesis in the ganglionic eminences and that modulates cortical neurogenesis. The results also suggest that HDACs may regulate the developmental switch from neurogenesis to astrogliogenesis that occurs in late gestation
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