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A. M. Mikhailov - One of the best experts on this subject based on the ideXlab platform.
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X-ray structures of Uridine phosphorylase from Vibrio cholerae in complexes with Uridine, thymidine, uracil, thymine, and Phosphate anion: Substrate specificity of bacterial Uridine phosphorylases
Crystallography Reports, 2016Co-Authors: I.i. Prokofev, Vladislav V. Balaev, Azat Gabdulkhakov, T. A. Seregina, Alexander S. Mironov, Alexander A. Lashkov, Ch. Betzel, A. M. MikhailovAbstract:In many types of human tumor cells and infectious agents, the demand for pyrimidine nitrogen bases increases during the development of the disease, thus increasing the role of the enzyme Uridine phosphorylase in metabolic processes. The rational use of Uridine phosphorylase and its ligands in pharmaceutical and biotechnology industries requires knowledge of the structural basis for the substrate specificity of the target enzyme. This paper summarizes the results of the systematic study of the three-dimensional structure of Uridine phosphorylase from the pathogenic bacterium Vibrio cholerae in complexes with substrates of enzymatic reactions—Uridine, Phosphate anion, thymidine, uracil, and thymine. These data, supplemented with the results of molecular modeling, were used to consider in detail the structural basis for the substrate specificity of Uridine phosphorylases. It was shown for the first time that the formation of a hydrogen-bond network between the 2′-hydroxy group of Uridine and atoms of the active-site residues of Uridine phosphorylase leads to conformational changes of the ribose moiety of Uridine, resulting in an increase in the reactivity of Uridine compared to thymidine. Since the binding of thymidine to residues of Uridine phosphorylase causes a smaller local strain of the β-N1-glycosidic bond in this the substrate compared to the Uridine molecule, the β-N1-glycosidic bond in thymidine is more stable and less reactive than that in Uridine. It was shown for the first time that the Phosphate anion, which is the second substrate bound at the active site, interacts simultaneously with the residues of the β5-strand and the β1-strand through hydrogen bonding, thus securing the gate loop in a conformation
I.i. Prokofev - One of the best experts on this subject based on the ideXlab platform.
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X-ray structures of Uridine phosphorylase from Vibrio cholerae in complexes with Uridine, thymidine, uracil, thymine, and Phosphate anion: Substrate specificity of bacterial Uridine phosphorylases
Crystallography Reports, 2016Co-Authors: I.i. Prokofev, Vladislav V. Balaev, Azat Gabdulkhakov, T. A. Seregina, Alexander S. Mironov, Alexander A. Lashkov, Ch. Betzel, A. M. MikhailovAbstract:In many types of human tumor cells and infectious agents, the demand for pyrimidine nitrogen bases increases during the development of the disease, thus increasing the role of the enzyme Uridine phosphorylase in metabolic processes. The rational use of Uridine phosphorylase and its ligands in pharmaceutical and biotechnology industries requires knowledge of the structural basis for the substrate specificity of the target enzyme. This paper summarizes the results of the systematic study of the three-dimensional structure of Uridine phosphorylase from the pathogenic bacterium Vibrio cholerae in complexes with substrates of enzymatic reactions—Uridine, Phosphate anion, thymidine, uracil, and thymine. These data, supplemented with the results of molecular modeling, were used to consider in detail the structural basis for the substrate specificity of Uridine phosphorylases. It was shown for the first time that the formation of a hydrogen-bond network between the 2′-hydroxy group of Uridine and atoms of the active-site residues of Uridine phosphorylase leads to conformational changes of the ribose moiety of Uridine, resulting in an increase in the reactivity of Uridine compared to thymidine. Since the binding of thymidine to residues of Uridine phosphorylase causes a smaller local strain of the β-N1-glycosidic bond in this the substrate compared to the Uridine molecule, the β-N1-glycosidic bond in thymidine is more stable and less reactive than that in Uridine. It was shown for the first time that the Phosphate anion, which is the second substrate bound at the active site, interacts simultaneously with the residues of the β5-strand and the β1-strand through hydrogen bonding, thus securing the gate loop in a conformation
Roland K O Sigel - One of the best experts on this subject based on the ideXlab platform.
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specific phosphorothioate substitution within domain 6 of a group ii intron ribozyme leads to changes in local structure and metal ion binding
Journal of Biological Inorganic Chemistry, 2018Co-Authors: Michele C Erat, Emina Besic, Michael Oberhuber, Silke Johannsen, Roland K O SigelAbstract:Group II introns are large self-splicing ribozymes that require high amounts of monovalent and divalent metal ions for folding and catalysis under in vitro conditions. Domain 6 of these ribozymes contains a highly conserved adenosine whose 2'-OH acts as a nucleophile during self-cleavage via the branching pathway. We have previously suggested a divalent metal ion that binds to the major groove at the GU wobble pair above the branch-A in a minimal, but active branch domain construct (D6-27) from the yeast mitochondrial intron Sc.ai5γ. Here we characterize metal ion binding to the Phosphate oxygens at the branch site. In vitro transcription yielded a D6-27 construct where all R P oxygens of the Uridine Phosphate groups are replaced by sulfur (α-thio-D6-27). We determined its NMR structure, the second RNA-only structure containing thioPhosphate groups. [31P] resonances were assigned and chemical shift changes monitored upon titration with Cd2+. In addition, the two Uridines flanking the branch-point, U19 and U21 were specifically thioated by chemical synthesis (thio-U19-D6-27 and thio-U19/U21-D6-27), enabling us to study Cd2+ binding at the R P-, as well as the S P- position of the corresponding Phosphate oxygens. Our studies reveal that both non-bridging Phosphate oxygens of U19 are involved in metal ion coordination, whereas only the major groove Phosphate oxygen of U21 is influenced. Together with NOE data of a hexaamminecobalt(III) titration, this suggests a single metal ion binding site at the GU wobble pair above the branch point in the major groove of D6 of this group II intron ribozyme.
Vladislav V. Balaev - One of the best experts on this subject based on the ideXlab platform.
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X-ray structures of Uridine phosphorylase from Vibrio cholerae in complexes with Uridine, thymidine, uracil, thymine, and Phosphate anion: Substrate specificity of bacterial Uridine phosphorylases
Crystallography Reports, 2016Co-Authors: I.i. Prokofev, Vladislav V. Balaev, Azat Gabdulkhakov, T. A. Seregina, Alexander S. Mironov, Alexander A. Lashkov, Ch. Betzel, A. M. MikhailovAbstract:In many types of human tumor cells and infectious agents, the demand for pyrimidine nitrogen bases increases during the development of the disease, thus increasing the role of the enzyme Uridine phosphorylase in metabolic processes. The rational use of Uridine phosphorylase and its ligands in pharmaceutical and biotechnology industries requires knowledge of the structural basis for the substrate specificity of the target enzyme. This paper summarizes the results of the systematic study of the three-dimensional structure of Uridine phosphorylase from the pathogenic bacterium Vibrio cholerae in complexes with substrates of enzymatic reactions—Uridine, Phosphate anion, thymidine, uracil, and thymine. These data, supplemented with the results of molecular modeling, were used to consider in detail the structural basis for the substrate specificity of Uridine phosphorylases. It was shown for the first time that the formation of a hydrogen-bond network between the 2′-hydroxy group of Uridine and atoms of the active-site residues of Uridine phosphorylase leads to conformational changes of the ribose moiety of Uridine, resulting in an increase in the reactivity of Uridine compared to thymidine. Since the binding of thymidine to residues of Uridine phosphorylase causes a smaller local strain of the β-N1-glycosidic bond in this the substrate compared to the Uridine molecule, the β-N1-glycosidic bond in thymidine is more stable and less reactive than that in Uridine. It was shown for the first time that the Phosphate anion, which is the second substrate bound at the active site, interacts simultaneously with the residues of the β5-strand and the β1-strand through hydrogen bonding, thus securing the gate loop in a conformation
Azat Gabdulkhakov - One of the best experts on this subject based on the ideXlab platform.
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X-ray structures of Uridine phosphorylase from Vibrio cholerae in complexes with Uridine, thymidine, uracil, thymine, and Phosphate anion: Substrate specificity of bacterial Uridine phosphorylases
Crystallography Reports, 2016Co-Authors: I.i. Prokofev, Vladislav V. Balaev, Azat Gabdulkhakov, T. A. Seregina, Alexander S. Mironov, Alexander A. Lashkov, Ch. Betzel, A. M. MikhailovAbstract:In many types of human tumor cells and infectious agents, the demand for pyrimidine nitrogen bases increases during the development of the disease, thus increasing the role of the enzyme Uridine phosphorylase in metabolic processes. The rational use of Uridine phosphorylase and its ligands in pharmaceutical and biotechnology industries requires knowledge of the structural basis for the substrate specificity of the target enzyme. This paper summarizes the results of the systematic study of the three-dimensional structure of Uridine phosphorylase from the pathogenic bacterium Vibrio cholerae in complexes with substrates of enzymatic reactions—Uridine, Phosphate anion, thymidine, uracil, and thymine. These data, supplemented with the results of molecular modeling, were used to consider in detail the structural basis for the substrate specificity of Uridine phosphorylases. It was shown for the first time that the formation of a hydrogen-bond network between the 2′-hydroxy group of Uridine and atoms of the active-site residues of Uridine phosphorylase leads to conformational changes of the ribose moiety of Uridine, resulting in an increase in the reactivity of Uridine compared to thymidine. Since the binding of thymidine to residues of Uridine phosphorylase causes a smaller local strain of the β-N1-glycosidic bond in this the substrate compared to the Uridine molecule, the β-N1-glycosidic bond in thymidine is more stable and less reactive than that in Uridine. It was shown for the first time that the Phosphate anion, which is the second substrate bound at the active site, interacts simultaneously with the residues of the β5-strand and the β1-strand through hydrogen bonding, thus securing the gate loop in a conformation
