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91.
W Dou S Mukherjee H Li M Venkatesh H Wang S Kortagere A Peleg SS Chilimuri ZT Wang Y Feng ER Fearon S Mani 《PloS one》2012,7(7):e36075
Pregnane X Receptor (PXR), a master regulator of drug metabolism and inflammation, is abundantly expressed in the gastrointestinal tract. Baicalein and its O-glucuronide baicalin are potent anti-inflammatory and anti-cancer herbal flavonoids that undergo a complex cycle of interconversion in the liver and gut. We sought to investigate the role these flavonoids play in inhibiting gut inflammation by an axis involving PXR and other potential factors. The consequences of PXR regulation and activation by the herbal flavonoids, baicalein and baicalin were evaluated in vitro in human colon carcinoma cells and in vivo using wild-type, Pxr-null, and humanized (hPXR) PXR mice. Baicalein, but not its glucuronidated metabolite baicalin, activates PXR in a Cdx2-dependent manner in vitro, in human colon carcinoma LS174T cells, and in the murine colon in vivo. While both flavonoids abrogate dextran sodium sulfate (DSS)-mediated colon inflammation in vivo, oral delivery of a potent bacterial β-glucuronidase inhibitor eliminates baicalin's effect on gastrointestinal inflammation by preventing the microbial conversion of baicalin to baicalien. Finally, reduction of gastrointestinal inflammation requires the binding of Cdx2 to a specific proximal site on the PXR promoter. Pharmacological targeting of intestinal PXR using natural metabolically labile ligands could serve as effective and potent therapeutics for gut inflammation that avert systemic drug interactions. 相似文献
92.
93.
Pregnane glycosides from Caralluma adscendens var. fimbriata 总被引:1,自引:0,他引:1
Kunert O Rao VG Babu GS Sujatha P Sivagamy M Anuradha S Rao BV Kumar BR Alex RM Schühly W Kühnelt D Rao GV Rao AV 《化学与生物多样性》2008,5(2):239-250
Eleven novel pregnane glycosides, 2-7 and 9-13, of which four, i.e., 10-13, comprised a new pregnane-type genin exhibiting a hydroxymethylene instead of a Me group at C(19), and the known pregnane glycoside stalagmoside V (8) were isolated from whole plants of Caralluma adscendens var. fimbriata, a native Indian succulent plant. Their structures were elucidated by extensive 2D-NMR spectroscopic studies. 相似文献
94.
95.
96.
We have carried out a systematic analysis in order to evaluate whether Intra-Chain Disulfide Bridged Peptides (ICDBPs) observed in proteins of known three-dimensional structure adopt structurally similar conformations as they may correspond to structural/functional motifs. 406 representative ICDBPs comprising between 3 to 17 amino acid residues could be classified according to peptide sequence length and main-chain secondary structure conformation into 146 classes. ICDBPs comprising 6 amino acid residues are maximally represented in the Protein Data Bank. They also represent the maximum number of main-chain secondary structure conformational classes. Individual ICDBPs in each class represent different protein superfamilies and correspond to different amino acid sequences. We identified 145 ICDBP pairs that had not less-than 0.5 A root mean square deviation value corresponding to their equivalent peptide backbone atoms. We believe these ICDBPs represent structural motifs and possible candidates in order to further explore their structure/function role in the corresponding proteins. The common conformational classes observed for ICDBPs defined according to the main-chain secondary structure conformations; H (helix), B (residue in a isolated beta bridge), C (coil), E (extended beta strand), G (3(10) helix), I (pi helix), S (bend), T (hydrogen-bonded turn) were; "CHHH", "CTTC", "CSSS" and "CSSC" (for ICDBP length 4), "CSSCC" (length 5), "EETTEE", "CCSSCC", "CCSSSC" (length 6), "EETTTEE" (length 7), "EETTTTEE" (length 8), "EEEETTEEEE" (length 10), "EEEETTTEEEE" (length 11) and "EEEETTTTEEEE" (length 12). 相似文献
97.
Albrecht M. Koppenhöfer Cesar R. Rodriguez-Saona Sridhar Polavarapu Robert J. Holdcraft 《Biocontrol Science and Technology》2008,18(1):21-31
A series of laboratory and greenhouse experiments evaluated the entomopathogenic nematodes Steinernema scarabaei Stock & Koppenhöfer, Heterorhabditis bacteriophora Poinar, and H. zealandica Poinar for control of second- and third-instar cranberry white grub, Phyllophaga georgiana Horn (Coleoptera: Scarabaeidae), in cranberries. Steinernema scarabaei was the most effective species with 76–100% control at a rate of 2.5×109 IJ/ha in the greenhouse experiments. H. zealandica and especially H. bacteriophora were generally less effective and required rates of 5×109 IJ/ha for acceptable control. Larval stage had no effect on H. zealandica and H. bacteriophora performance, whereas S. scarabaei was more effective against third instars than second instars in the laboratory but not in the greenhouse experiments. Steinernema scarabaei, should it become commercially available, could be an effective alternative to chemical insecticides for P. georgiana management. 相似文献
98.
In this research, the B3LYP density functional and Stevens effective core potentials are used to compare carbon-hydrogen and carbon-heteroatom bond activation by an iridium(I) complex. Of particular importance is to address the kinetic (transition state) and thermodynamic (ground state) selectivity. The complex Ir(PH3)2(H) with CH3-X (X=F, Cl, OH, SH, NH2, PH2) as the substrate has been used as a model. Good agreement in geometries is obtained between the target molecules and experimental models. The resultant products of C-H and C-X oxidative addition are Y-shaped minima (i.e., a distorted trigonal bipyramid with one acute and two obtuse angles among the equatorial ligands). Oxidative addition of the C-X bond to the substrate is exothermic for groups 16 and 17, but endothermic for group 15. A significant thermodynamic preference for C-X activation over C-H activation is observed for these Ir(I) complexes. However, analysis of the transition states for oxidative addition suggests that there is a kinetic preference for C-H activation. 相似文献
99.
Characterization of the functional interaction of adipocyte lipid-binding protein with hormone-sensitive lipase. 总被引:4,自引:0,他引:4
W J Shen Y Liang R Hong S Patel V Natu K Sridhar A Jenkins D A Bernlohr F B Kraemer 《The Journal of biological chemistry》2001,276(52):49443-49448
Hormone-sensitive lipase (HSL) is an intracellular lipase that plays an important role in the hydrolysis of triacylglycerol in adipose tissue. HSL has been shown to interact with adipocyte lipid-binding protein (ALBP), a member of the family of intracellular lipid-binding proteins that bind fatty acids and other hydrophobic ligands. The current studies have addressed the functional significance of the association and mapped the site of interaction between HSL and ALBP. Incubation of homogeneous ALBP with purified, recombinant HSL in vitro resulted in a 2-fold increase in substrate hydrolysis. Moreover, the ability of oleate to inhibit HSL hydrolytic activity was attenuated by co-incubation with ALBP. Co-transfection of Chinese hamster ovary cells with HSL and ALBP resulted in greater hydrolytic activity than transfection of cells with HSL and vector alone. Deletional mutations of HSL localized the region of HSL that interacts with ALBP to amino acids 192-200, and site-directed mutagenesis of individual amino acids in this region identified His-194 and Glu-199 as critical for mediating the interaction of HSL with ALBP. Interestingly, HSL mutants H194L and E199A, each of which retained normal basal hydrolytic activity, failed to display an increase in hydrolytic activity when co-transfected with wild type ALBP. Therefore, ALBP increases the hydrolytic activity of HSL through its ability to bind and sequester fatty acids and via specific protein-protein interaction. Thus, HSL and ALBP constitute a functionally important lipolytic complex. 相似文献
100.
Kiyoto Kamagata Yuji Itoh Cheng Tan Eriko Mano Yining Wu Sridhar Mandali Shoji Takada Reid
C Johnson 《Nucleic acids research》2021,49(15):8642
Architectural DNA-binding proteins (ADBPs) are abundant constituents of eukaryotic or bacterial chromosomes that bind DNA promiscuously and function in diverse DNA reactions. They generate large conformational changes in DNA upon binding yet can slide along DNA when searching for functional binding sites. Here we investigate the mechanism by which ADBPs diffuse on DNA by single-molecule analyses of mutant proteins rationally chosen to distinguish between rotation-coupled diffusion and DNA surface sliding after transient unbinding from the groove(s). The properties of yeast Nhp6A mutant proteins, combined with molecular dynamics simulations, suggest Nhp6A switches between two binding modes: a static state, in which the HMGB domain is bound within the minor groove with the DNA highly bent, and a mobile state, where the protein is traveling along the DNA surface by means of its flexible N-terminal basic arm. The behaviors of Fis mutants, a bacterial nucleoid-associated helix-turn-helix dimer, are best explained by mobile proteins unbinding from the major groove and diffusing along the DNA surface. Nhp6A, Fis, and bacterial HU are all near exclusively associated with the chromosome, as packaged within the bacterial nucleoid, and can be modeled by three diffusion modes where HU exhibits the fastest and Fis the slowest diffusion. 相似文献