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991.
Modulation of substrate preference of thermus maltogenic amylase by mutation of the residues at the interface of a dimer 总被引:1,自引:0,他引:1
Park SH Kang HK Shim JH Woo EJ Hong JS Kim JW Oh BH Lee BH Cha H Park KH 《Bioscience, biotechnology, and biochemistry》2007,71(6):1564-1567
To elucidate the relationship between the substrate size and geometric shape of the catalytic site of Thermus maltogenic amylase, Gly50, Asp109, and Val431, located at the interface of the dimer, were replaced with bulky amino acids. The k(cat)/K(m) value of the mutant for amylose increased significantly, whereas that for amylopectin decreased as compared to that of the wild-type enzyme. Thus, the substituted bulky amino acid residues modified the shape of the catalytic site, such that the ability of the enzyme to distinguish between small and large molecules like amylose and amylopectin was enhanced. 相似文献
992.
Park HS Park JT Kang HK Cha H Kim DS Kim JW Park KH 《Bioscience, biotechnology, and biochemistry》2007,71(5):1348-1352
A treX in the trehalose biosynthesis gene cluster of Sulfolobus solfataricus ATCC 35092 has been reported to produce TreX, which hydrolyzes the alpha-1,6-branch portion of amylopectin and glycogen. TreX exhibited 4-alpha-D-glucan transferase activity, catalyzing the transfer of alpha-1,4-glucan oligosaccharides from one molecule to another in the case of linear maltooligosaccharides (G3-G7), and it produced cyclic glucans from amylopectin and amylose like 4-alpha-glucanotransferase. These results suggest that TreX is a novel isoamylase possessing the properties of 4-alpha-glucanotransferase. 相似文献
993.
Alexandra Michurina M Sadman Sakib Cemil Kerimoglu Dennis Manfred Krüger Lalit Kaurani Md Rezaul Islam Parth Devesh Joshi Sophie Schrder Tonatiuh Pena Centeno Jiayin Zhou Ranjit Pradhan Julia Cha Xingbo Xu Gregor Eichele Elisabeth M Zeisberg Andrea Kranz A Francis Stewart Andr Fischer 《The EMBO journal》2022,41(1)
In mammals, histone 3 lysine 4 methylation (H3K4me) is mediated by six different lysine methyltransferases. Among these enzymes, SETD1B (SET domain containing 1b) has been linked to syndromic intellectual disability in human subjects, but its role in the mammalian postnatal brain has not been studied yet. Here, we employ mice deficient for Setd1b in excitatory neurons of the postnatal forebrain, and combine neuron‐specific ChIP‐seq and RNA‐seq approaches to elucidate its role in neuronal gene expression. We observe that Setd1b controls the expression of a set of genes with a broad H3K4me3 peak at their promoters, enriched for neuron‐specific genes linked to learning and memory function. Comparative analyses in mice with conditional deletion of Kmt2a and Kmt2b histone methyltransferases show that SETD1B plays a more pronounced and potent role in regulating such genes. Moreover, postnatal loss of Setd1b leads to severe learning impairment, suggesting that SETD1B‐dependent regulation of H3K4me levels in postnatal neurons is critical for cognitive function. 相似文献
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Jennifer Chean Charng-Jui Chen Gabriel Gugiu Patty Wong Seung Cha Harry Li Tung Nguyen Supriyo Bhatticharya John E. Shively 《The Journal of biological chemistry》2021,297(5)
Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is expressed in the liver and secreted as biliary glycoprotein 1 (BGP1) via bile canaliculi (BCs). CEACAM1-LF is a 72 amino acid cytoplasmic domain mRNA splice isoform with two immunoreceptor tyrosine-based inhibitory motifs (ITIMs). Ceacam1−/− or Ser503Ala transgenic mice have been shown to develop insulin resistance and nonalcoholic fatty liver disease; however, the role of the human equivalent residue, Ser508, in lipid dysregulation is unknown. Human HepG2 hepatocytes that express CEACAM1 and form BC in vitro were compared with CEACAM1−/− cells and CEACAM1−/− cells expressing Ser508Ala null or Ser508Asp phosphorylation mimic mutations or to phosphorylation null mutations in the tyrosine ITIMs known to be phosphorylated by the tyrosine kinase Src. CEACAM1−/− cells and the Ser508Asp and Tyr520Phe mutants strongly retained lipids, while Ser508Ala and Tyr493Phe mutants had low lipid levels compared with wild-type cells, indicating that the ITIM mutants phenocopied the Ser508 mutants. We found that the fatty acid transporter CD36 was upregulated in the S508A mutant, coexpressed in BCs with CEACAM1, co-IPed with CEACAM1 and Src, and when downregulated via RNAi, an increase in lipid droplet content was observed. Nuclear translocation of CD36 associated kinase LKB1 was increased sevenfold in the S508A mutant versus CEACAM1−/− cells and correlated with increased activation of CD36-associated kinase AMPK in CEACAM1−/− cells. Thus, while CEACAM1−/− HepG2 cells upregulate lipid storage similar to Ceacam1−/− in murine liver, the null mutation Ser508Ala led to decreased lipid storage, emphasizing evolutionary changes between the CEACAM1 genes in mouse and humans. 相似文献
996.
Gregory J. Wiepz Jon C. D. Houtman Donald Cha Paul J. Bertics 《Journal of cellular physiology》1997,173(1):44-53
Growth hormone (GH) has previously been reported to influence the adipose conversion of 3T3-F442A murine fibroblasts, partly by causing these cells to exit the cell cycle and to become unresponsive to serum-stimulated mitogenesis. To better understand this process, quiescent fibroblasts were treated with fully stimulatory doses (50 nM) of epidermal growth factor (EGF) in the presence or absence of pituitary human GH (hGH) or the phorbol ester phorbol 12-myristate 13-acetate (PMA), which is known to down-regulate EGF receptor activity. EGF-induced DNA synthesis was attenuated by hGH in a dose-dependent manner with an ED50 of approximately 0.1 nM and a maximally effective dose of 10–30 nM. This effect appeared to be the result of inhibition of DNA synthesis and exclusive of a time shift in the initiation of the S phase of the cell cycle. Additionally, insulin-like growth factor-1 (IGF-1), which can act as an important in vivo mediator of GH, failed to mimic the anti-mitogenic effects of GH. The ability of hGH to antagonize EGF-stimulated mitogenesis did not appear to be due to the down-regulation of EGF receptor mass or to pronounced changes in EGF-induced tyrosine kinase activity. Furthermore, when GH was administered at various times after EGF addition, GH continued to be effective at inhibiting EGF-induced DNA synthesis for up to 9 hr after EGF treatment. Modulation of EGF-induced cell cycle progression was further evidenced by the ability of GH to promote a marked decrease in the EGF-induced expression of D cyclins. In comparison, PMA inhibited EGF-induced DNA synthesis for up to 18 hr after EGF addition and also down-regulated EGF receptor mass and activity; these observations suggest that the mechanism of GH action is largely distinct from that of PMA. We conclude that GH can selectively and dose-dependently modulate EGF receptor-mediated DNA synthesis exclusive of any rapid or extensive effects on EGF receptor mass or tyrosine kinase activity. Furthermore, the capacity of GH to attenuate EGF-induced mitogenesis, even when administered 9 hr after EGF addition, and the GH modulation of EGF-induced expression of D cyclins, suggest that there are GH-induced effects on systems involved in the transition of these fibroblasts through the G1 phase of the cell cycle. In sum, these data support a specific interaction of this somatotropic hormone/cytokine with EGF in the control of cell cycle progression in 3T3-F442A fibroblasts. J. Cell. Physiol. 173:44–53, 1997. © 1997 Wiley-Liss, Inc. 相似文献
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1000.
Ceruloplasmin, a blue multi-copper alpha(2)-glycoprotein found in the plasma of all vertebrates, is capable of oxidizing aromatic amines and ferrous iron. Here, we report that human ceruloplasmin exhibits an alkyl hydroperoxide peroxidase activity, which is independent of the oxidase activity. The site-specific modification of the sulfhydryl of cysteine at position 699 in ceruloplasmin completely abolished the antioxidant activity, suggesting that ceruloplasmin is a peroxidase with a cysteinyl thiol as a functional nucleophile. The crystal structure of human ceruloplasmin reveals that the domain containing Cys-699 is apart from the multi-copper complex domains. Taken together, these data suggest that ceruloplasmin has a distinct active site for a glutathione-linked peroxidase activity apart from the copper complex site exerting ferroxidase activity. 相似文献