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51.
A putative LysR‐type transcriptional regulator PrhO positively regulates the type III secretion system and contributes to the virulence of Ralstonia solanacearum 下载免费PDF全文
52.
Tensho Ten Satoru Nagatoishi Ryo Maeda Masaru Hoshino Yoshiaki Nakayama Motoharu Seiki Takeharu Sakamoto Kouhei Tsumoto 《The Journal of biological chemistry》2021,297(5)
Mint3 is known to enhance aerobic ATP production, known as the Warburg effect, by binding to FIH-1. Since this effect is considered to be beneficial for cancer cells, the interaction is a promising target for cancer therapy. However, previous research has suggested that the interacting region of Mint3 with FIH-1 is intrinsically disordered, which makes investigation of this interaction challenging. Therefore, we adopted thermodynamic and structural studies in solution to clarify the structural and thermodynamical changes of Mint3 binding to FIH-1. First, using a combination of circular dichroism, nuclear magnetic resonance, and hydrogen/deuterium exchange–mass spectrometry (HDX-MS), we confirmed that the N-terminal half, which is the interacting part of Mint3, is mostly disordered. Next, we revealed a large enthalpy and entropy change in the interaction of Mint3 using isothermal titration calorimetry (ITC). The profile is consistent with the model that the flexibility of disordered Mint3 is drastically reduced upon binding to FIH-1. Moreover, we performed a series of ITC experiments with several types of truncated Mint3s, an effective approach since the interacting part of Mint3 is disordered, and identified amino acids 78 to 88 as a novel core site for binding to FIH-1. The truncation study of Mint3 also revealed the thermodynamic contribution of each part of Mint3 to the interaction with FIH-1, where the core sites contribute to the affinity (ΔG), while other sites only affect enthalpy (ΔH), by forming noncovalent bonds. This insight can serve as a foothold for further investigation of intrinsically disordered regions (IDRs) and drug development for cancer therapy. 相似文献
53.
Youhei Takagi Kouhei Matsui Haruaki Nobori Haruka Maeda Akihiko Sato Takeshi Kurosu Yasuko Orba Hirofumi Sawa Kazunari Hattori Kenichi Higashino Yoshito Numata Yutaka Yoshida 《Bioorganic & medicinal chemistry letters》2017,27(15):3586-3590
NS2B-NS3 protease is an essential enzyme for the replication of dengue virus (DENV), which continues to be a serious threat to worldwide public health. We designed and synthesized a series of cyclic peptides mimicking the substrates of this enzyme, and assayed their activity against the DENV-2 NS2B-NS3 protease. The introduction of aromatic residues at the appropriate positions and conformational restriction generated the most promising cyclic peptide with an IC50 of 0.95 μM against NS2B-NS3 protease. Cyclic peptides with proper positioning of additional arginines and aromatic residues exhibited antiviral activity against DENV. Furthermore, replacing the C-terminal amide bond of the polybasic amino acid sequence with an amino methylene moiety stabilized the cyclic peptides against hydrolysis by NS2B-NS3 protease, while maintaining their enzyme inhibitory activity and antiviral activity. 相似文献
54.
Tatsuyuki Yamashita Makoto Ashiuchi Kouhei Ohnishi Shin-ichiro Kato Shinji Nagata Haruo Misono 《Journal of Molecular Catalysis .B, Enzymatic》2003,23(2-6):213
Bifidobacterium bifidum is a useful probiotic agent exhibiting health-promoting properties, and its peptidoglycans have the potential for applications in the fields of food science and medicine. We investigated the bifidobacterial alanine racemase, which is essential in the synthesis of
-alanine as an essential component of the peptidoglycans. Alanine racemase was purified to homogeneity from a crude extract of B. bifidum NBRC 14252. It consisted of two identical subunits with a molecular mass of 50 kDa. The enzyme required pyridoxal 5′-phosphate (PLP) as a coenzyme. The activity was lost in the presence of a thiol-modifying agent. The enzyme almost exclusively catalyzed the alanine racemization; other amino acids tested, except for serine, were inactive as substrates. The kinetic parameters of the enzyme suggested that the B. bifidum alanine racemase possesses comparatively low affinities for both the coenzyme (9.1 μM for PLP) and substrates (44.3 mM for
-alanine; 74.3 mM for
-alanine). The alr gene encoding the alanine racemase was cloned and sequenced. The alr gene complemented the
-alanine auxotrophy of Escherichia coli MB2795, and an abundant amount of the enzyme was produced in cells of the E. coli MB2795 clone. The enzymologic and kinetic properties of the purified recombinant enzyme were almost the same as those of the alanine racemase from B. bifidum NBRC 14252. 相似文献
55.
Kenji Nomiya Kuniaki Onodera Ken Tsukagoshi Kouhei Shimada Akira Yoshizawa Tada-aki Itoyanagi Akiyoshi Sugie Shinichiro Tsuruta Ryo Sato Noriko Chikaraishi Kasuga 《Inorganica chimica acta》2009,362(1):43-55
Metal-oxygen bonding complexes (M = MgII, MnII, NiII, MoVI, WVI, PdII, SbIII, BiIII, FeIII, TiIV, KI, BaII, ZrIV and HfIV) with a hinokitiol (Hhino; 2-hydroxy-4-isopropylcyclohepta-2,4,6-trienone or β-thujaplicin) ligand, which has two unequivalent oxygen donor atoms, were synthesized and characterized by elemental analysis, TG/DTA, FT-IR and solution (1H and 13C) NMR spectroscopy. Single-crystal X-ray structure analysis revealed various molecular structures for the complexes, which were classified into several families of family, i.e. type A [MII(hino)2(L)]2 (M = MgII, MnII, NiII; L = EtOH or MeOH), with a dimeric structure consisting of one bridging hino− anion, one chelating hino− anion and one alcohol or water molecule, type B, with the octahedral, cis-dioxo, bis-chelate complexes cis-[MVIO2(hino)2] (M = MoVI, WVI), type C, with square planar complex [MII(hino)2] (M = PdII), type D, with tris-chelate, 7-coordinate complexes with one inert electron pair [MIII(hino)3] (M = SbIII, BiIII), type D′, with the bis-chelate, pseudo-6-coordinate complexes with one inert electron pair [MIII(hino)2X] (M = SbIII, X = Br), type E, with tris-chelate, 6-coordinate complexes with Δ and Λ isomers [MIII(hino)3] (M = FeIII), type E′ of bis-chelate, 6-coordinate complex [MIV(hino)2X2] (M = TiIV, X = Cl), type F, with water-soluble alkali metal salts [MI(hino)] (M = KI), and type H, with tetrakis-chelate, 8-coordinate complexes [MIV(hino)4](M = ZrIV, HfIV). These structural features were compared with those of metal complexes with a related ligand, tropolone (Htrop). The antimicrobial activities of these complexes, evaluated in terms of minimum inhibitory concentration (MIC; μg mL−1) in two systems, were compared to elucidate the relationship between structure and antimicrobial activity. 相似文献
56.
Melanin-concentrating hormone (MCH), originally discovered in the teleost pituitary, is a hypothalamic neuropeptide involved in the regulation of body color in fish. Although MCH is also present in the mammalian brain, it has no evident function in providing pigmentation. Instead, this peptide is now recognized to be one of the key neuropeptides that act as appetite enhancers in mammals such as rodents and primates. Although there has been little information about the central action of MCH on appetite in fish, recent studies have indicated that, in goldfish, MCH acts as an anorexigenic neuropeptide, modulating the α-melanocyte-stimulating hormone signaling pathway through neuronal interaction. These observations indicate that there may be major differences in the mode of action of MCH between fish and mammals. This paper reviews what is currently known about the regulation of food intake by MCH in fish, especially the goldfish. 相似文献
57.
58.
LPS-induced ROS generation and changes in glutathione level and their relation to the maturation of human monocyte-derived dendritic cells 总被引:7,自引:0,他引:7
Lipopolysaccharide (LPS)-induced reactive oxygen species (ROS) generation and the concomitant decline in the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG) were demonstrated in human monocyte-derived dendritic cells (DC). Further, their relation to the maturation of DC, characterized by the production of cytokines, up-regulation of cell surface molecules and allo-stimulatory capacity, was examined. The LPS-induced ROS generation was demonstrated using electron paramagnetic resonance spectroscopy in intact cells, and was also confirmed using laser scanning confocal microscopy. The GSH/GSSG was assesed using a glutathione assay kit. When the DC were treated with alpha-phenyl-tert-butylnitrone, the ROS generation was attenuated, but the declined GSH/GSSG was not attenuated, and only cytokine production was suppressed among the above-mentioned maturation characteristics. When the DC were treated with glutathione monoethyl ester, both the ROS generation and the declined GSH/GSSG were attenuated, and the maturation characteristics were all suppressed. These findings suggest that the LPS-induced ROS generation and the concomitant decline in GSH/GSSG occur in human monocyte-derived DC and that the former is involved in cytokine production, while the latter is involved in the up-regulation of cell surface molecules and allo-stimulatory capacity. Since the cytokine production and the allo-stimulatory capacity of DC play an important role in inflammatory and immune responses, differential regulation of the ROS generation and the declined GSH/GSSG may be useful as therapeutic tools in diseases where both responses become entangled, such as sepsis and graft-versus-host disease. 相似文献
59.
60.
Watanabe K Shuto T Sato M Onuki K Mizunoe S Suzuki S Sato T Koga T Suico MA Kai H Ikeda T 《Biochemical and biophysical research communications》2011,(1):18-24
The Ganoderma lucidum (G. lucidum) is one of the oriental fungi that has been reported to have immunomodulatory properties. Although effect of β-glucans from G. lucidum has been well documented, little is known about how other major bioactive components, the triterpenes, contribute to the immunomodulatory function of G. lucidum. Here, we showed that triterpenes-rich extract of antlered form of G. lucidum (G. lucidum AF) induces TNFα production in monocytic THP-1 cells. Furthermore, the extract also synergized with lipopolysaccharide (LPS) to induce TNFα production in THP-1 cells, suggesting an immunostimulatory role of triterpenes-rich extract of G. lucidum AF. Notably, the extract enhanced LPS-induced phosphorylation of p38 mitogen-activated protein kinase (MAPK), while it suppressed LPS-induced phosphorylation of c-Jun N-terminal kinase (JNK) MAPK. p38 Inhibitor suppressed TNFα production, while JNK inhibitor enhanced TNFα production, implying that synergistic effect of the extract may work by modulating p38 and JNK MAPKs. Moreover, we found that the triterpenes-rich extract of G. lucidum AF contains high amounts of lucidenic acids. Lucidenic acid-A, -F and -D2, which seem to dominantly exist in the extract, were purified from the triterpenes-rich extract. We also identified Lucidenic acid-A and -F as modulators of JNK and p38, respectively. Thus, our data demonstrate that lucidenic acids-rich extract from G. lucidum AF enhances LPS-induced immune responses in monocytic THP-1 cells possibly via the modulation of p38 and JNK MAPKs activation. 相似文献