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排序方式: 共有262条查询结果,搜索用时 15 毫秒
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Chemical modification of chalcone isomerase by mercurials and tetrathionate. Evidence for a single cysteine residue in the active site 总被引:1,自引:0,他引:1
R A Bednar W B Fried Y W Lock B Pramanik 《The Journal of biological chemistry》1989,264(24):14272-14276
Chalcone isomerase from soybean is inactivated by stoichiometric amounts of p-mercuribenzoate or HgCl2. Spectral titration of the enzyme with p-mercuribenzoate indicates that a single thiol group is modified. Treatment of modified enzyme with KCN or thiols results in a complete restoration of enzyme activity demonstrating that the inactivation is not due to irreversible protein denaturation. A product of the enzymatic reaction, naringenin, provides complete kinetic protection against inactivation by both mercurials. The binding constant (33 microM) for naringenin determined from the concentration dependence of the protection agrees with the inhibition constant (34 microM) for naringenin as a competitive inhibitor of the catalytic reaction. This agreement demonstrates that the observed kinetic protection results from the specific binding of naringenin to the active site. Incubation of native chalcone isomerase with sodium tetrathionate (0.1 M) results in a slow time-dependent loss of enzymatic activity. The inactivation of chalcone isomerase by tetrathionate and N-ethylmaleimide becomes very rapid in the presence of 6 M urea, indicating that the native tertiary structure is responsible for the low reactivity of the enzymatic thiol. The stoichiometric modification of reduced and denatured chalcone isomerase by [3H] N-ethylmaleimide indicates that the enzyme contains only a single cysteine residue and does not contain any disulfides. The evidence presented suggests that the only half-cystine residue in chalcone isomerase is located in the active site and thereby provides the first clue to the location of the active site in chalcone isomerase. 相似文献
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After propagation of Rhizopus javanicus in defined media containing glucose, urea, and mineral salts in deionized distilled water, the ability of the nonliving biomass to sequester cupric ion was assayed. Growth, uptake capacity (saturation uptake at >1 mM Cu2+ concentration in solution), and biosorptive yield (biomass concentration × uptake capacity) were increased by augmentation of the growth medium with mineral salts once growth was under way. In the stationary phase, the uptake capacity of mycelia, which were normally a poor biosorbent, was improved within 4 h of trace metal addition to the growth medium. Growth of the culture was inhibited by excessive concentrations (0.04 to 40 μM) of metals in the medium in the following order: Cu > Co ≥ Ni > Mn > Mo; zinc was not inhibitory at 40 μM, and chromium was stimulatory at 0.53 μM but slightly inhibitory at higher levels. Iron and potassium phosphate stimulated growth at levels of 0.53 and 40 mM, respectively. When R. javanicus was propagated in a medium with a high salt concentration, exponential growth (0.23 h−1) to a biomass concentration of >3 g/liter and a biosorptive yield of >500 μmol/liter was achieved. It is evident that the powerful biosorbent characteristics of Rhizopus biomass led to depletion of available trace minerals in suspension culture, which in turn limited growth. 相似文献
4.
Chalcone isomerase form soybean is inactivated by treatment with diethyl pyrocarbonate (DEP). The competitive inhibitor 4',4-dihydroxychalcone provides kinetic protection against inactivation by DEP with a binding constant at the site of protection in agreement with its binding constant at the active site. Very high concentrations of the competitive inhibitors 4',4-dihydroxychalcone or morin hydrate offer a 10- to 40-fold maximal protection, suggesting a second slower mechanism for inactivation which cannot be prevented by blockage of the active site. Blockage of the only cysteine residue in chalcone isomerase with p-mercuribenzoate does not affect the rate constant for DEP-dependent inactivation and indicates that the modification of the cysteine residue is not responsible for the activity loss observed in the presence of DEP. Treatment of inactivated enzyme with hydroxylamine does not restore catalytic activity, indicating that the modification of histidine or tyrosine residues is not responsible for the activity loss. All five histidines of chalcone isomerase are modified by DEP at pH 5.7 and ionic strength 1.0 M. The rate constant for the modification of the histidine residues of chalcone isomerase is close to that for the reaction of N-acetyl histidine with DEP, indicating that the histidine residues are quite accessible to the modifying reagent. The rate of histidine modification is the same in native enzyme, in urea-denatured enzyme, and in the presence of a competitive inhibitor. In the presence of the competitive inhibitor morin hydrate, all of the histidine residues of chalcone isomerase can be modified without significant loss in catalytic activity. These results demonstrate that the histidine residues of chalcone isomerase are not essential for catalysis and therefore cannot function as nucleophilic catalysts as previously proposed. 相似文献
5.
Two new adenosine analogs, 2-(2-bromoethyl) adenosine monophosphate and 3-(2-bromoethyl) adenosine monophosphate, were synthesized, purified by semipreparative high-pressure liquid chromatography, and completely characterized. A new synthesis of 5-(2-bromoethyl) adenosine monophosphate is presented which facilitates the preparation of radioactive reagent with label either in the ethyl group or the purine ring of the nucleotide derivative. The reactive moiety of these derivatives, a bromoalkyl group, has the ability to react with the nucleophilic side chains of several amino acids. The second-order, pH-independent rate constants for reaction with the side chains of the amino acids cysteine, lysine, histidine, and tyrosine were determined as 3×10–4, 6×10–6, 3×10–7, and <1×10–7 M–1 sec–1, respectively. These data could be use in estimating the rate enhancement observed in modification of a protein by these affinity-labeling reagents. 5-(S-(2-hydroxyethyl)cysteine) adenosine monophosphate, the derivative expected from exhaustive digestion of protein in which a cysteinyl residue is modified by 5-(2-bromoethyl) adenosine monophosphate, and S-2-hydroxyethyl)cysteine, the derivative anticipated upon acid hydrolysis of such a modified protein, were synthesized, characterized, and their elution positions from an amino acid analyzer determined. These bromoethyl AMP derivatives are potential affinity labels for enzymes that bind 2-, 3-, or 5-nucleotides such as TPN, coenzyme A, or ADP, respectively. 相似文献
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Katja Paul Minli Wang Emil Mladenov Alena Bencsik-Theilen Theresa Bednar Wenqi Wu Hiroshi Arakawa George Iliakis 《PloS one》2013,8(3)
Biochemical and genetic studies suggest that vertebrates remove double-strand breaks (DSBs) from their genomes predominantly by two non-homologous end joining (NHEJ) pathways. While canonical NHEJ depends on the well characterized activities of DNA-dependent protein kinase (DNA-PK) and LIG4/XRCC4/XLF complexes, the activities and the mechanisms of the alternative, backup NHEJ are less well characterized. Notably, the contribution of LIG1 to alternative NHEJ remains conjectural and although biochemical, cytogenetic and genetic experiments implicate LIG3, this contribution has not been formally demonstrated. Here, we take advantage of the powerful genetics of the DT40 chicken B-cell system to delineate the roles of LIG1 and LIG3 in alternative NHEJ. Our results expand the functions of LIG1 to alternative NHEJ and demonstrate a remarkable ability for LIG3 to backup DSB repair by NHEJ in addition to its essential function in the mitochondria. Together with results on DNA replication, these observations uncover a remarkable and previously unappreciated functional flexibility and interchangeability between LIG1 and LIG3. 相似文献
9.
Swati P. Mercer Anthony J. Roecker Susan Garson Duane R. Reiss C. Meacham Harrell Kathy L. Murphy Joseph G. Bruno Rodney A. Bednar Wei Lemaire Donghui Cui Tamara D. Cabalu Cuyue Tang Thomayant Prueksaritanont George D. Hartman Steven D. Young Christopher J. Winrow John J. Renger Paul J. Coleman 《Bioorganic & medicinal chemistry letters》2013,23(24):6620-6624
The orexin (or hypocretin) system has been identified as a novel target for the treatment of insomnia due to the wealth of biological and genetic data discovered over the past decade. Recently, clinical proof-of-concept was achieved for the treatment of primary insomnia using dual (OX1R/OX2R) orexin receptor antagonists. However, elucidation of the pharmacology associated with selective orexin-2 receptor antagonists (2-SORAs) has been hampered by the lack of orally bioavailable, highly selective small molecule probes. Herein, the discovery and optimization of a novel series of 2,5-diarylnicotinamides as potent and orally bioavailable orexin-2 receptor selective antagonists is described. A compound from this series demonstrated potent sleep promotion when dosed orally to EEG telemetrized rats. 相似文献
10.
Anna Myná?ová Ivona Foitová Martin Kvá? Dana Květoňová Michael Rost Helen Morrogh-Bernard Wisnu Nurcahyo Cathleen Nguyen Supriyadi Supriyadi Bohumil Sak 《PloS one》2016,11(3)