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101.
A. V. Veselovsky E. G. Matveeva N. N. Zolotov A. S. Ivanov 《Molecular simulation》2013,39(4-6):411-419
Abstract The prolylendopeptidase (PEP) is the proteolytic enzyme, which plays an essential role in the regulation of some processes in central nervous system, such as memory, learning and behavior. It was shown that PEP activity changes at different diseases, like Parkinsons or Alzheimer's diseases, and some PEP inhibitors are used in therapy. At present time the discovery of new types of PEP inhibitors are the actual task. In this study the structure of PEP active site was analyzed by 3D-QSAR with CoMFA methods using of 12 PEP substrates. The designed pharmacophore model assumes that substrates interact with PEP active site by pyrrolidol ring of proline residue and by hydrogen bonding. The 3-D-QSAR + CoMFA model of PEP substrates propose that the hydrophobic bonds play the essential role in substrate interaction with enzyme. This model reveals the important steric and electrostatic areas around the molecules and the presence of substituents controls the PEP activity for substrates. Analysis of obtained data allows to assume, that substrate binding in PEP active site causes essential perturbations of substrate structure. This effect mainly depends on chemical nature of the amino acid side chain, located near to proline. 相似文献
102.
Hervé Poras Sophie DuquesnoyMarie-Claude Fournié-Zaluski Céline Ratinaud-GiraudBernard P. Roques Tanja Ouimet 《Analytical biochemistry》2013,441(2):152-161
Leukotriene A4 hydrolase (LTA4H) is a bifunctional zinc-dependent metalloprotease bearing both an epoxide hydrolase, producing the pro-inflammatory LTB4 leukotriene, and an aminopeptidase activity, whose physiological relevance has long been ignored. Distinct substrates are commonly used for each activity, although none is completely satisfactory; LTA4, substrate for the hydrolase activity, is unstable and inactivates the enzyme, whereas aminoacids β-naphthylamide and para-nitroanilide, used as aminopeptidase substrates, are poor and nonselective. Based on the three-dimensional structure of LTA4H, we describe a new, specific, and high-affinity fluorigenic substrate, PL553 [l-(4-benzoyl)phenylalanyl-β-naphthylamide], with both in vitro and in vivo applications. PL553 possesses a catalytic efficiency (kcat/Km) of 3.8 ± 0.5 × 104 M−1 s−1 using human recombinant LTA4H and a limit of detection and quantification of less than 1 to 2 ng. The PL553 assay was validated by measuring the inhibitory potency of known LTA4H inhibitors and used to characterize new specific amino-phosphinic inhibitors. The LTA4H inhibition measured with PL553 in mouse tissues, after intravenous administration of inhibitors, was also correlated with a reduction in LTB4 levels. This authenticates the assay as the first allowing the easy measurement of endogenous LTA4H activity and in vitro specific screening of new LTA4H inhibitors. 相似文献
103.
Meilan Huang Zhuo Li Dawei Li Steven Walker Caroline Greenan Richard Kennedy 《Bioorganic & medicinal chemistry letters》2013,23(10):3044-3050
We identified nine small-molecule hit compounds of Heat shock 70 kDa protein 5 (HSPA5) from cascade in silico screening based on the binding modes of the tetrapeptides derived from the peptide substrate or inhibitors of Escherichia coli HSP70. Two compounds exhibit promising inhibition activities from cancer cell viability and tumor inhibition assays. The binding modes of the hit compounds provide a platform for development of selective small molecule inhibitors of HSPA5. 相似文献
104.
Yoshiyuki Takasaki 《Bioscience, biotechnology, and biochemistry》2013,77(8):1523-1530
A β-amylase and a pullulanase produced by Bacillus cereus var. mycoides were purified by means of ammonium sulfate fractionation, adsorption on starch and celite and Sephadex G–100 column chromatography. The purified enzymes were homogeneous in disc electrophoresis.The β-amylase released only maltose from amylose, amylopectin, starch and glycogen, and the released maltose was in β-form. The pullulanase released maltose, maltotriose and maltotetraose from β-limit dextrin and maltotriose from pullulan, but not amylose-like substance from amylopectin.The optimum pHs of β-amylase and pullulanase were about 7 and 6~6.5, respectively. The optimum temperatures of the enzymes were about 50°C. The enzymes were inhibited by the sulfhydryl reagents such as mercuric chloride and p-chloromercuribenzoate, and the inhibitions with p-chloromercuribenzoate were restored by the addition of cysteine. The molecular weights of β-amylase and pullulanase were estimated to be 35,000±5,000 and 110,000±20,000, respectively. 相似文献
105.
Hiromichi Nagasawa Akira Isogai Akinori Suzuki Saburo Tamura 《Bioscience, biotechnology, and biochemistry》2013,77(8):1759-1763
13C-NMR spectra of isoechinulins A, B and C, metabolites from Aspergillus ruber, were fully assigned on the basis of chemical shifts and multiplicities and comparison with their analogues. Taking advantage of the symmetrical structure of the diketopiperazine ring, the stereochemistry of the trisubstituted carbon-carbon double bond in a dehydrotryptophyl moiety was determined as Z (cis) by measuring the coupling constants, , in the proton nondecoupled spectrum of isoechinulin B. 相似文献
106.
Hitoshi Ohmori Hisashi Ishitani Kazuyoshi Sato Shoichi Shimizu Saburo Fukui 《Bioscience, biotechnology, and biochemistry》2013,77(2):359-365
Purple nonsulfur bacteria, Rhodospirillum rubrum and Rhodopseudomonas spheroides were found to possess coenzyme B12-dependent glutamate mutase activity. Cell-free extracts of these bacteria grown on Co2+-containing media catalyzed the conversion of glutamate to β-methylaspartate and further to mesaconate. The activity of the cell-free extracts of these organisms cultivated on Co2+-deficient media was markedly lower than that of the normal cells. Addition of coenzyme B12 to the former reaction mixture enhanced the mesaconate formation via β-methylaspartate. These results indicate the involvement of coenzyme Independent glutamate mutase of these bacteria in the dissimilation of glutamate to acetyl-CoA and pyruvate through the following pathway.glutamate→β→methylaspartate→mesaconate→citramalate→→acetyl-CoA, pyruvate On the other hand, a greater part of glutamate was converted to α-hydroxyglutarate and succinate with the cell-free extracts of these photosynthetic bacteria. This fact, taking account of the presence of propionyl-CoA carboxylase in these bacteria, implies the participation of coenzyme B12-dependent (R)-methylmalonyl-CoA mutase in the formation of succinate via the following route.glutamate→α-ketoglutarate→α-hydroxyglutarate→propionate→propionyl-CoA→(S)-methylmalonyl-CoA→(R)-methylmalonyl-CoA→succinyl-CoA 相似文献
107.
Kei Yamanaka 《Bioscience, biotechnology, and biochemistry》2013,77(10):2035-2037
Previously a cyclic pathway for the partial oxidation of propionyl-CoA to pyruvate has been proposed. Enzymatic evidence for the presence of the key reactions involved in this pathway is described and discussed herein. The condensation of propionyl-CoA with oxaloacetate into methylcitrate is shown to be catalyzed by an enzyme contained in cell-free extracts of Candida lipolytica; the enzyme seems to differ from the usual citrate synthase. Methylcitrate is easily convertible to a mixture of C7-acids by the action of cell-free extract of the mutant strain. On the other hand, a similar mixture is changed into pyruvate and succinate by the action of cell-free extract of the parent strain. Evidence is given that methylisocitrate, one of the products of the conversion, is mainly cleaved by the action of an additional enzyme other than the usual isocitrate lyase. The accumulation of methylisocitrate in a large amount from odd-carbon n-alkanes by the mutant strain can be safely ascribed to the absence or a low level of this enzyme in the mutant strain. 相似文献
108.
《Bioscience, biotechnology, and biochemistry》2013,77(12):2038-2042
Deoxy derivatives of p-nitrophenyl (PNP) α-d-mannopyranoside, PNP 2-deoxy-α-d-arabino-hexopyranoside, 3-deoxy-α-d-arabino-hexopyranoside, 4-deoxy-α-d-lyxo-hexopyranoside, and α-d-rhamnopyranoside, were synthesized and hydrolytic activities of jack bean and almond α-mannosidases against them were investigated. These α-mannosidases scarcely acted on the 2-, 3-, and 4-deoxy derivatives, while the 6-deoxy one was hydrolyzed by the enzymes as fast as PNP α-d-mannopyranoside, which is a common substrate for α-mannosidase. These results indicate that the hydroxyl groups at C-2, 3, and 4 of the mannopyranoside are necessary to be recognized as a substrate by these enzymes, while that at C-6 does not have so a crucial role in substrate discrimination. Values of Km and Vmax of the enzymes on the hydrolysis of PNP α-d-rhamnopyranoside were obtained from kinetic studies. 相似文献
109.
An α-glucosidase and a glucoamylase have been isolated from fruit bodies of Lentinus edodes (Berk.) Sing., by a procedure including fractionation with ammonium sulfate, DEAE-cellulose column chromatography, and preparative gel electrofocusing. Both of them were homogeneous on gel electrofocusing and ultracentrifugation. The molecular weight of α-glucosidase and glucoamylase was 51,000 and 55,000, respectively. The α-glucosidase hydrolyzed maltose, maltotriose, phenyl α-maltoside, amylose, and soluble starch, but did not act on sucrose. The glucoamylase hydrolyzed maltose, maltotriose, phenyl α-maltoside, soluble starch, amylose, amylopectin, and glycogen, glucose being the sole product formed in the digests of these substrates. Both enzymes hydrolyzed phenyl a-maltoside into glucose and phenyl α-glucoside. The glucoamylase hydrolyzed soluble starch, amylose, amylopectin, and glycogen, converting them almost completely into glucose. It was found that β-glucose was liberated from amylose by the action of glucoamylase, while α-glucose was produced by the α-glucosidase.Maltotriose was the main α-glucosyltransfer product formed from maltose by the α-glucosidase. 相似文献
110.
Hiroshi Meguro Toshio Konno Katura Tuzimura 《Bioscience, biotechnology, and biochemistry》2013,77(4):945-947
Antifungal activities were examined and compared for some 40 kinds of aliphatic and aromatic aldehydes, alcohols, phenolic compounds, ether compounds and hydrocarbons from essential oils and for some related compounds, using seven fungi. 相似文献