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1.
A beta-glucosidase/beta-galactosidase with Mr 52,500 was isolated from calf liver cytosol by a four-step procedure incorporating affinity chromatography on N-(9-carboxynonyl)-deoxynojirimycin-AH-Sepharose. Its pH optimum was at 5.8 with half-maximal activity at pH 3.5 and 8.6. Affinity for gluco compounds expressed by Km or Ki of substrates and inhibitors was 2- to 10-fold higher than for the corresponding galacto compounds. Alkyl glucosides were hydrolyzed with lower Vmax than p-nitrophenyl and 4-methylumbelliferyl glucosides, but due to their higher affinity the alkyl glucosides displayed values for kcat/Km of the same magnitude of the aryl glucosides when the alkyl chains were longer than octyl. Glucosylsphingosine was bound with Ki (= Km) 2.2 microM and hydrolyzed with a Vmax that was 50-fold lower than the Vmax for 4-methylumbelliferyl beta-glucoside. The product sphingosine was inhibitory with Ki 0.30 microM. A systematic study with alkyl glucosides and glucosylamines defined the aglycon site as a narrow, strongly hydrophobic cleft able to accommodate up to 10 methylene groups. Each CH2 group contributed 3.1 kJ/mol to the standard free energy of binding. The inhibition by gluco- and galactosylamine and by 1-deoxynojirimycin and its D-galacto analog was approximately 200-fold better than by corresponding nonbasic compounds. pH dependence of the inhibition and comparison with permanently cationic glycosyl derivatives showed that the nonprotonated form was the inhibiting species. This feature puts the cytosolic beta-glucosidase in the large class of glycoside hydrolases which strongly bind basic glycosyl derivatives by their protonation at the active site and formation of a shielded ion pair with the carboxylate of an aspartic or glutamic side chain. 相似文献
2.
Characterization of calf liver glucosidase I and its inhibition by basic sugar analogs 总被引:4,自引:0,他引:4
Glucosidase I, the enzyme catalyzing the first step of N-linked oligosaccharide processing, has been purified from calf liver crude membranes [H. Hettkamp, G. Legler, and E. Bause, (1984) Eur. J. Biochem. 142, 85-90]. Binding experiments with concanavalin A-Sepharose suggest that glucosidase I is a glycoprotein with high-mannose carbohydrate chain(s). The enzyme has a subunit molecular mass of approximately 83 kDa and specifically hydrolyzes the terminal alpha-1,2-linked glucose residue from the natural Glc3-Man9-GlcNAc2 oligosaccharide. Studies with a variety of substrates modified in the aglycon moiety suggest that the Glc2 branch rather than the more distant domains of the substrate molecule are important for binding and hydrolysis. Glucosidase I does not require metal ions for activity and is strongly inhibited by 1-deoxynojirimycin (dNM) and its N-alkyl derivatives. Ki values range from 0.07 microM for N-methyl-dNM to 1.0 microM for dNM, measured at the pH-optimum of enzyme activity. The pH dependence of inhibition indicates that the cationic form of the inhibitors is the active species. Comparison of the Ki for N-decanoyl-dNM (approximately 70 microM) with that of N-decyl-dNM (approximately 0.4 microM) suggests that electrostatic interactions at the catalytic site of the enzyme are important for inhibitor binding. 1-Deoxymannojirimycin, previously assumed to be a specific mannosidase inhibitor, as well as its N-methyl and N-5-carboxypentyl derivatives, inhibit glucosidase I with Ki values around 190, 17, and 100 microM, respectively. This apparent lack of specificity shows that in vivo experiments on N-glycoprotein processing as well as the interpretation of results with these mannosidase inhibitors may give misleading results when these compounds are used in the millimolar range. 相似文献
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Background
Owing to rapid expansion of protein structure databases in recent years, methods of structure comparison are becoming increasingly effective and important in revealing novel information on functional properties of proteins and their roles in the grand scheme of evolutionary biology. Currently, the structural similarity between two proteins is measured by the root-mean-square-deviation (RMSD) in their best-superimposed atomic coordinates. RMSD is the golden rule of measuring structural similarity when the structures are nearly identical; it, however, fails to detect the higher order topological similarities in proteins evolved into different shapes. We propose new algorithms for extracting geometrical invariants of proteins that can be effectively used to identify homologous protein structures or topologies in order to quantify both close and remote structural similarities. 相似文献6.
7.
Wei-Hsin Chen Ching-Liang Hsieh Chun-Ping Huang Tzu-Jou Lin Jason TC Tzen Tin-Yun Ho Yi-Wen Lin 《Journal of biomedical science》2011,18(1):82
Background
Peripheral tissue inflammation initiates hyperalgesia accompanied by tissue acidosis, nociceptor activation, and inflammation mediators. Recent studies have suggested a significantly increased expression of acid-sensing ion channel 3 (ASIC3) in both carrageenan- and complete Freund's adjuvant (CFA)-induced inflammation. This study tested the hypothesis that acupuncture is curative for mechanical hyperalgesia induced by peripheral inflammation. 相似文献8.
Inhibition of N-linked oligosaccharide trimming does not interfere with surface expression of certain integral membrane proteins 总被引:15,自引:3,他引:15 下载免费PDF全文
The effects of 1-deoxynojirimycin (dNM) and 1-deoxymannojirimycin (dMM), inhibitors of oligosaccharide trimming glucosidase I and mannosidase I, respectively, on the biosynthesis of vesicular stomatitis virus G protein, influenza virus hemagglutinin, and human class I histocompatibility antigens were investigated. Although the oligosaccharides of these membrane glycoproteins were greatly altered, neither dNM nor dMM interferred with their surface expression, as determined by a variety of assays, including accessibility to proteases and antibodies; neither did these drugs inhibit production of infectious virus particles. 相似文献
9.
Jade George Jaimee R. Compton Dagmar H. Leary Mark A. Olson Patricia M. Legler 《Proteins》2014,82(11):3101-3116
Camelid single domain antibodies (sdAb) are known for their thermal stability and reversible refolding. We have characterized an unusually stable sdAb recognizing Staphylococcal enterotoxin B with one of the highest reported melting temperatures (Tm = 85°C). Unexpectedly, ~10?20% of the protein formed a dimer in solution. Three other cases where <20% of the sdAb dimerized have been reported; however, this is the first report of both the monomeric and dimeric X‐ray crystal structures. Concentration of the monomer did not lead to the formation of new dimer suggesting a stable conformationally distinct species in a fraction of the cytoplasmically expressed protein. Comparison of periplasmic and cytoplasmic expression showed that the dimer was associated with cytoplasmic expression. The disulfide bond was partially reduced in the WT protein purified from the cytoplasm and the protein irreversibly unfolded. Periplasmic expression produced monomeric protein with a fully formed disulfide bond and mostly reversible refolding. Crystallization of a disulfide‐bond free variant, C22A/C99V, purified from the periplasm yielded a structure of a monomeric form, while crystallization of C22A/C99V from the cytoplasm produced an asymmetric dimer. In the dimer, a significant conformational asymmetry was found in the loop residues of the edge β‐strands (S50‐Y60) containing the highly variable complementarity determining region, CDR2. Two dimeric assemblies were predicted from the crystal packing. Mutation of a residue at one of the interfaces, Y98A, disrupted the dimer in solution. The pleomorphic homodimer may yield insight into the stability of misfolded states and the importance of the conserved disulfide bond in preventing their formation. Proteins 2014; 82:3101–3116. © 2014 Wiley Periodicals, Inc. 相似文献
10.
Aerobic biodegradation of methyl tert-butyl ether by aquifer bacteria from leaking underground storage tank sites. 总被引:3,自引:0,他引:3
S R Kane H R Beller T C Legler C J Koester H C Pinkart R U Halden A M Happel 《Applied and environmental microbiology》2001,67(12):5824-5829
The potential for aerobic methyl tert-butyl ether (MTBE) degradation was investigated with microcosms containing aquifer sediment and groundwater from four MTBE-contaminated sites characterized by oxygen-limited in situ conditions. MTBE depletion was observed for sediments from two sites (e.g., 4.5 mg/liter degraded in 15 days after a 4-day lag period), whereas no consumption of MTBE was observed for sediments from the other sites after 75 days. For sediments in which MTBE was consumed, 43 to 54% of added [U-(14)C]MTBE was mineralized to (14)CO(2). Molecular phylogenetic analyses of these sediments indicated the enrichment of species closely related to a known MTBE-degrading bacterium, strain PM1. At only one site, the presence of water-soluble gasoline components significantly inhibited MTBE degradation and led to a more pronounced accumulation of the metabolite tert-butyl alcohol. Overall, these results suggest that the effects of oxygen and water-soluble gasoline components on in situ MTBE degradation will vary from site to site and that phylogenetic analysis may be a promising predictor of MTBE biodegradation potential. 相似文献