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Stepan A. Kremis Dmitry S. Baev Alla V. Lipeeva Elvira E. Shults Tatiana G. Tolstikova Olga I. Sinitsyna Alexey V. Kochetov Tatiana S. Frolova 《Journal of biochemical and molecular toxicology》2019,33(11)
The furocoumarin backbone is a promising platform for chemical modifications aimed at creating new pharmaceutical agents. However, the high level of biological activity of furocoumarins is associated with a number of negative effects. For example, some of the naturally occurring ones and their derivatives can show genotoxic and mutagenic properties as a result of their forming crosslinks with DNA molecules. Therefore, a particularly important area for the chemical modification of natural furocoumarins is to reduce the negative aspects of their bioactivity. By studying a group of 21 compounds—1,2,3‐triazolyl modified derivatives of furocoumarin and peucedanin—using the SOS chromotest, the Ames test, and DNA‐comet assays, we revealed modifications that can neutralize the structure's genotoxic properties. Theoretical aspects of the interaction of the compound library were studied using molecular modeling and this identified the leading role of the polyaromatic molecular core that takes part in stacking‐interactions with the pi‐systems of the nitrogenous bases of DNA. 相似文献
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Sevostyanova IA Solovjeva ON Kochetov GA 《Biochemical and biophysical research communications》2004,313(3):771-774
Yeast transketolase, in addition to catalyzing the transferase reaction through utilization of two substrates--the donor substrate (ketose) and the acceptor substrate (aldose)--is also able to catalyze a one-substrate reaction with only aldose (glycolaldehyde) as substrate. The interaction of glycolaldehyde with holotransketolase results in formation of the transketolase reaction intermediate, dihydroxyethyl-thiamin diphosphate. Then the glycolaldehyde residue is transferred from dihydroxyethyl-thiamin diphosphate to free glycolaldehyde. As a result, the one-substrate transketolase reaction product, erythrulose, is formed. The specific activity of transketolase was found to be 0.23 U/mg and the apparent Km for glycolaldehyde was estimated as 140 mM. 相似文献
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With the example of yeast genes, context organization was compared for functional gene regions (promoter, 5'-UTR, 3'-UTR) and tested for association with the level of gene expression. Several parameters (nucleotide composition, dinucletoide content bias) proved to correlate with expression level, each functional region having its specific features. Context optimization of a functional region was assumed to be essential for highly efficient interaction with the expression system of the cell. Specific context features were considered as dispersed signals important for high-level gene expression. 相似文献
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Solovjeva ON Sevostyanova IA Yurshev VA Selivanov VA Kochetov GA 《The protein journal》2012,31(2):137-140
Catalytic activity has been demonstrated for holotransketolase in the absence of free bivalent cations in the medium. The
two active centers of the enzyme are equivalent in both the catalytic activity and the affinity for the substrates. In the
presence of free Ca2+ (added to the medium from an external source), this equivalence is lost: negative cooperativity is induced on binding of
either xylulose 5-phosphate (donor substrate) or ribose 5-phosphate (acceptor substrate), whereupon the catalytic conversion
of the bound substrates causes the interaction between the centers to become positively cooperative. Moreover, the enzyme
total activity increase is observed. 相似文献
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Kolodiazgnaia IaS Titov SE Kochetov AV Trifonova EA Romanova AV Komarova ML Koval' VS Shumnyĭ VK 《Genetika》2007,43(7):994-998
Analysis of resistance of genetically modified tobacco plants bearing antisense suppressor of proline dehydrogenase gene and characterized with higher content of proline to elevated concentrations of heavy metals was performed. It was demonstrated that progeny of transgenic plants have high resistance to lead, nickel and cadmium ions. 相似文献
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Solov'eva ON Meshalkina LE Kovina MV Selivanov VA Bykova IA Kochetov GA 《Biochemistry. Biokhimii?a》2000,65(10):1202-1205
Two substrates of the transketolase reaction are known to bind with the enzyme according to a ping-pong mechanism [1]. It is shown in this work that high concentrations of ribose-5-phosphate (acceptor substrate) compete with xylulose-5-phosphate (donor substrate), suppressing the transketolase activity (Ki = 3.8 mM). However, interacting with the donor-substrate binding site on the protein molecule, the acceptor substrate, unlike the donor substrate, does not cause any change in the active site of the enzyme. The data are interesting in terms of studying the regulatory mechanism of the transketolase activity and the structure of the enzyme-substrate complex. 相似文献
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AUG codons at the beginning of protein coding sequences are frequent in eukaryotic mRNAs with a suboptimal start codon context 总被引:3,自引:0,他引:3
Kochetov AV 《Bioinformatics (Oxford, England)》2005,21(7):837-840
MOTIVATION: The translation start site plays an important role in the control of translation efficiency of eukaryotic mRNAs. However, mRNAs with a suboptimal context of start AUG codon are relatively abundant. It is likely that at least some mRNAs with suboptimal start codon context contain the other signals providing additional information for efficient AUG recognition. RESULTS: Frequency of AUG codons at the beginning of the coding part of eukaryotic mRNAs was analyzed in relation to the context of translation start codon. It was found that the observed downstream AUG content in the mRNAs with optimal start codon context was close to the expected value, whereas it was significantly higher in the mRNAs with a suboptimal context. It is likely that downstream AUG codons can often be utilized as additional start sites to increase translation rate of mRNAs with a suboptimal context of the annotated start codon and many eukaryotic proteins can be characterized by some N-end heterogeneity. 相似文献