The Experts below are selected from a list of 321 Experts worldwide ranked by ideXlab platform
Jerzy Leszczynski - One of the best experts on this subject based on the ideXlab platform.
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interaction of nucleic acid bases and watson crick base pairs with fullerene computational study
Chemical Physics Letters, 2010Co-Authors: M. K. Shukla, Eugene Zakar, Madan Dubey, Raju R Namburu, Jerzy LeszczynskiAbstract:Abstract A first-principle investigation using the recently developed M05-2X density functional and the 6-311++G(d, p) basis set was performed to understand the nature of interaction between C60 and nucleic acid bases and the Watson–Crick base pairs. It was found that C60 forms stacking complexes with nucleic acid bases and base pairs. It was revealed that the strength of interaction of nucleic acid bases with C60 follows the order: G > C > A > T > U, while the GC base pair forms stronger complex than the AT base pair with C60.
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dft investigation of the interaction of gold nanoclusters with nucleic acid base guanine and the watson crick guanine cytosine base pair
Journal of Physical Chemistry C, 2009Co-Authors: M. K. Shukla, Eugene Zakar, Madan Dubey, Jerzy LeszczynskiAbstract:The interaction of gold nanoclusters (Aun, n = 2, 4, 6, 8, 10, 12) with nucleic acid purine base guanine (G) and the Watson−Crick guanine-cytosine (GC) base pair through the major groove site (N7 site of guanine) of DNA was investigated theoretically. Geometries of complexes were optimized at the density functional theory (DFT) level employing the hybrid B3LYP functional. The 6-31G(d) basis set was used for all atoms except gold, for which the LANL2DZ effective core potential (ECP) was used. Natural population analysis was performed to determine NBO charges. The vertical first ionization potential and electron affinity of guanine and the guanine-cytosine base pair and their complexes with gold nanoclusters were also analyzed. It was revealed that gold clusters interact more strongly with the GC base pair than with isolated guanine. It was found that consequent to the binding of gold nanoclusters a substantial amount of electronic charge was transferred from guanine (or the guanine-cytosine base pair) to t...
Gregory L Verdine - One of the best experts on this subject based on the ideXlab platform.
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structural basis for the lesion scanning mechanism of the muty dna glycosylase
Journal of Biological Chemistry, 2017Co-Authors: Lan Wang, Srinivas Chakravarthy, Gregory L VerdineAbstract:Abstract The highly mutagenic A:oxoG (8-oxoguanine) base-pair is generated mainly by misreplication of the C:oxoG base-pair, the oxidation product of the C:G base-pair. A:oxoG base-pair is particularly insidious because neither base in it carries faithful information to direct the repair of the other. The bacterial MutY (MUTYH in humans) adenine DNA glycosylase is able to initiate the repair of A:oxoG by selectively cleaving the A base from the A:oxoG base-pair. The difference between faithful repair and wreaking mutagenic havoc on the genome lies in the accurate discrimination between two structurally similar base-pairs: A:oxoG and A:T. Here we present two crystal structures of the MutY N-terminal domain in complex with either undamaged DNA or DNA containing an intrahelical lesion. These structures have captured for the first time, a DNA glycosylase scanning the genome for a damaged base in the very first stage of lesion-recognition and the base-extrusion pathway. The mode of interaction observed here has suggested a common lesion-scanning mechanism across the entire helix-hairpin-helix superfamily to which MutY belongs. In addition, small-angle X-ray scattering (SAXS) studies together with accompanying biochemical assays have suggested a possible role played by the C-terminal oxoG-recognition domain of MutY in lesion-scanning.
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structural basis for the lesion scanning mechanism of the muty dna glycosylase
Journal of Biological Chemistry, 2017Co-Authors: Lan Wang, Srinivas Chakravarthy, Gregory L VerdineAbstract:The highly mutagenic A:8-oxoguanine (oxoG) base pair is generated mainly by misreplication of the C:oxoG base pair, the oxidation product of the C:G base pair. The A:oxoG base pair is particularly insidious because neither base in it carries faithful information to direct the repair of the other. The bacterial MutY (MUTYH in humans) adenine DNA glycosylase is able to initiate the repair of A:oxoG by selectively cleaving the A base from the A:oxoG base pair. The difference between faithful repair and wreaking mutagenic havoc on the genome lies in the accurate discrimination between two structurally similar base pairs: A:oxoG and A:T. Here we present two crystal structures of the MutY N-terminal domain in complex with either undamaged DNA or DNA containing an intrahelical lesion. These structures have captured for the first time a DNA glycosylase scanning the genome for a damaged base in the very first stage of lesion recognition and the base extrusion pathway. The mode of interaction observed here has suggested a common lesion-scanning mechanism across the entire helix-hairpin-helix superfamily to which MutY belongs. In addition, small angle X-ray scattering studies together with accompanying biochemical assays have suggested a possible role played by the C-terminal oxoG-recognition domain of MutY in lesion scanning.
Ichiro Hirao - One of the best experts on this subject based on the ideXlab platform.
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unnatural base pair systems toward the expansion of the genetic alphabet in the central dogma
Proceedings of the Japan Academy. Series B Physical and biological sciences, 2012Co-Authors: Ichiro Hirao, Michiko KimotoAbstract:Toward the expansion of the genetic alphabet of DNA, several artificial third base pairs (unnatural base pairs) have been created. Synthetic DNAs containing the unnatural base pairs can be amplified faithfully by PCR, along with the natural A-T and G-C pairs, and transcribed into RNA. The unnatural base pair systems now have high potential to open the door to next generation biotechnology. The creation of unnatural base pairs is a consequence of repeating "proof of concept" experiments. In the process, initially designed base pairs were modified to address their weak points. Some of them were artificially evolved to ones with higher efficiency and selectivity in polymerase reactions, while others were eliminated from the analysis. Here, we describe the process of unnatural base pair development, as well as the tests of their applications.
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a new unnatural base pair system between fluorophore and quencher base analogues for nucleic acid based imaging technology
Journal of the American Chemical Society, 2010Co-Authors: Michiko Kimoto, Tsuneo Mitsui, Akira Sato, Shigeyuki Yokoyama, Rie Yamashige, Ichiro HiraoAbstract:In the development of orthogonal extra base pairs for expanding the genetic alphabet, we created novel, unnatural base pairs between fluorophore and quencher nucleobase analogues. We found that the nucleobase analogue, 2-nitropyrrole (denoted by Pn), and its 4-substitutions, such as 2-nitro-4-propynylpyrrole (Px) and 4-[3-(6-aminohexanamido)-1-propynyl]-2-nitropyrrole (NH2-hx-Px), act as fluorescence quenchers. The Pn and Px bases specifically pair with their pairing partner, 7-(2,2′-bithien-5-yl)imidazo[4,5-b]pyridine (Dss), which is strongly fluorescent. Thus, these unnatural Dss−Pn and Dss−Px base pairs function as reporter−quencher base pairs, and are complementarily incorporated into DNA by polymerase reactions as a third base pair in combination with the natural A-T and G-C pairs. Due to the static contact quenching, the Pn and Px quencher bases significantly decreased the fluorescence intensity of Dss by the unnatural base pairings in DNA duplexes. In addition, the Dss−Px pair exhibited high effici...
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an unnatural base pair system for efficient pcr amplification and functionalization of dna molecules
Nucleic Acids Research, 2009Co-Authors: Michiko Kimoto, Tsuneo Mitsui, Rie Kawai, Shigeyuki Yokoyama, Ichiro HiraoAbstract:Toward the expansion of the genetic alphabet, we present an unnatural base pair system for efficient PCR amplification, enabling the site-specific incorporation of extra functional components into DNA. This system can be applied to conventional PCR protocols employing DNA templates containing unnatural bases, natural and unnatural base triphosphates, and a 3′→5′ exonuclease-proficient DNA polymerase. For highly faithful and efficient PCR amplification involving the unnatural base pairing, we identified the natural-base sequences surrounding the unnatural bases in DNA templates by an in vitro selection technique, using a DNA library containing the unnatural base. The system facilitates the site-specific incorporation of a variety of modified unnatural bases, linked with functional groups of interest, into amplified DNA. DNA fragments (0.15 amol) containing the unnatural base pair can be amplified 107-fold by 30 cycles of PCR, with <1% total mutation rate of the unnatural base pair site. Using the system, we demonstrated efficient PCR amplification and functionalization of DNA fragments for the extremely sensitive detection of zeptomol-scale target DNA molecules from mixtures with excess amounts (pmol scale) of foreign DNA species. This unnatural base pair system will be applicable to a wide range of DNA/RNA-based technologies.
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an unnatural hydrophobic base pair system site specific incorporation of nucleotide analogs into dna and rna
Nature Methods, 2006Co-Authors: Ichiro Hirao, Michiko Kimoto, Tsuneo Mitsui, Tsuyoshi Fujiwara, Rie Kawai, Akira Sato, Yoko Harada, Shigeyuki YokoyamaAbstract:Methods for the site-specific incorporation of extra components into nucleic acids can be powerful tools for creating DNA and RNA molecules with increased functionality. We present an unnatural base pair system in which DNA containing an unnatural base pair can be amplified and function as a template for the site-specific incorporation of base analog substrates into RNA via transcription. The unnatural base pair is formed by specific hydrophobic shape complementation between the bases, but lacks hydrogen bonding interactions. In replication, this unnatural base pair exhibits high selectivity in combination with the usual triphosphates and modified triphosphates, gamma-amidotriphosphates, as substrates of 3' to 5' exonuclease-proficient DNA polymerases, allowing PCR amplification. In transcription, the unnatural base pair complementarity mediates the incorporation of these base substrates and their analogs, such as a biotinylated substrate, into RNA by T7 RNA polymerase (RNAP). With this system, functional components can be site-specifically incorporated into a large RNA molecule.
Michiko Kimoto - One of the best experts on this subject based on the ideXlab platform.
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unnatural base pair systems toward the expansion of the genetic alphabet in the central dogma
Proceedings of the Japan Academy. Series B Physical and biological sciences, 2012Co-Authors: Ichiro Hirao, Michiko KimotoAbstract:Toward the expansion of the genetic alphabet of DNA, several artificial third base pairs (unnatural base pairs) have been created. Synthetic DNAs containing the unnatural base pairs can be amplified faithfully by PCR, along with the natural A-T and G-C pairs, and transcribed into RNA. The unnatural base pair systems now have high potential to open the door to next generation biotechnology. The creation of unnatural base pairs is a consequence of repeating "proof of concept" experiments. In the process, initially designed base pairs were modified to address their weak points. Some of them were artificially evolved to ones with higher efficiency and selectivity in polymerase reactions, while others were eliminated from the analysis. Here, we describe the process of unnatural base pair development, as well as the tests of their applications.
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a new unnatural base pair system between fluorophore and quencher base analogues for nucleic acid based imaging technology
Journal of the American Chemical Society, 2010Co-Authors: Michiko Kimoto, Tsuneo Mitsui, Akira Sato, Shigeyuki Yokoyama, Rie Yamashige, Ichiro HiraoAbstract:In the development of orthogonal extra base pairs for expanding the genetic alphabet, we created novel, unnatural base pairs between fluorophore and quencher nucleobase analogues. We found that the nucleobase analogue, 2-nitropyrrole (denoted by Pn), and its 4-substitutions, such as 2-nitro-4-propynylpyrrole (Px) and 4-[3-(6-aminohexanamido)-1-propynyl]-2-nitropyrrole (NH2-hx-Px), act as fluorescence quenchers. The Pn and Px bases specifically pair with their pairing partner, 7-(2,2′-bithien-5-yl)imidazo[4,5-b]pyridine (Dss), which is strongly fluorescent. Thus, these unnatural Dss−Pn and Dss−Px base pairs function as reporter−quencher base pairs, and are complementarily incorporated into DNA by polymerase reactions as a third base pair in combination with the natural A-T and G-C pairs. Due to the static contact quenching, the Pn and Px quencher bases significantly decreased the fluorescence intensity of Dss by the unnatural base pairings in DNA duplexes. In addition, the Dss−Px pair exhibited high effici...
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an unnatural base pair system for efficient pcr amplification and functionalization of dna molecules
Nucleic Acids Research, 2009Co-Authors: Michiko Kimoto, Tsuneo Mitsui, Rie Kawai, Shigeyuki Yokoyama, Ichiro HiraoAbstract:Toward the expansion of the genetic alphabet, we present an unnatural base pair system for efficient PCR amplification, enabling the site-specific incorporation of extra functional components into DNA. This system can be applied to conventional PCR protocols employing DNA templates containing unnatural bases, natural and unnatural base triphosphates, and a 3′→5′ exonuclease-proficient DNA polymerase. For highly faithful and efficient PCR amplification involving the unnatural base pairing, we identified the natural-base sequences surrounding the unnatural bases in DNA templates by an in vitro selection technique, using a DNA library containing the unnatural base. The system facilitates the site-specific incorporation of a variety of modified unnatural bases, linked with functional groups of interest, into amplified DNA. DNA fragments (0.15 amol) containing the unnatural base pair can be amplified 107-fold by 30 cycles of PCR, with <1% total mutation rate of the unnatural base pair site. Using the system, we demonstrated efficient PCR amplification and functionalization of DNA fragments for the extremely sensitive detection of zeptomol-scale target DNA molecules from mixtures with excess amounts (pmol scale) of foreign DNA species. This unnatural base pair system will be applicable to a wide range of DNA/RNA-based technologies.
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an unnatural hydrophobic base pair system site specific incorporation of nucleotide analogs into dna and rna
Nature Methods, 2006Co-Authors: Ichiro Hirao, Michiko Kimoto, Tsuneo Mitsui, Tsuyoshi Fujiwara, Rie Kawai, Akira Sato, Yoko Harada, Shigeyuki YokoyamaAbstract:Methods for the site-specific incorporation of extra components into nucleic acids can be powerful tools for creating DNA and RNA molecules with increased functionality. We present an unnatural base pair system in which DNA containing an unnatural base pair can be amplified and function as a template for the site-specific incorporation of base analog substrates into RNA via transcription. The unnatural base pair is formed by specific hydrophobic shape complementation between the bases, but lacks hydrogen bonding interactions. In replication, this unnatural base pair exhibits high selectivity in combination with the usual triphosphates and modified triphosphates, gamma-amidotriphosphates, as substrates of 3' to 5' exonuclease-proficient DNA polymerases, allowing PCR amplification. In transcription, the unnatural base pair complementarity mediates the incorporation of these base substrates and their analogs, such as a biotinylated substrate, into RNA by T7 RNA polymerase (RNAP). With this system, functional components can be site-specifically incorporated into a large RNA molecule.
M. K. Shukla - One of the best experts on this subject based on the ideXlab platform.
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interaction of nucleic acid bases and watson crick base pairs with fullerene computational study
Chemical Physics Letters, 2010Co-Authors: M. K. Shukla, Eugene Zakar, Madan Dubey, Raju R Namburu, Jerzy LeszczynskiAbstract:Abstract A first-principle investigation using the recently developed M05-2X density functional and the 6-311++G(d, p) basis set was performed to understand the nature of interaction between C60 and nucleic acid bases and the Watson–Crick base pairs. It was found that C60 forms stacking complexes with nucleic acid bases and base pairs. It was revealed that the strength of interaction of nucleic acid bases with C60 follows the order: G > C > A > T > U, while the GC base pair forms stronger complex than the AT base pair with C60.
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dft investigation of the interaction of gold nanoclusters with nucleic acid base guanine and the watson crick guanine cytosine base pair
Journal of Physical Chemistry C, 2009Co-Authors: M. K. Shukla, Eugene Zakar, Madan Dubey, Jerzy LeszczynskiAbstract:The interaction of gold nanoclusters (Aun, n = 2, 4, 6, 8, 10, 12) with nucleic acid purine base guanine (G) and the Watson−Crick guanine-cytosine (GC) base pair through the major groove site (N7 site of guanine) of DNA was investigated theoretically. Geometries of complexes were optimized at the density functional theory (DFT) level employing the hybrid B3LYP functional. The 6-31G(d) basis set was used for all atoms except gold, for which the LANL2DZ effective core potential (ECP) was used. Natural population analysis was performed to determine NBO charges. The vertical first ionization potential and electron affinity of guanine and the guanine-cytosine base pair and their complexes with gold nanoclusters were also analyzed. It was revealed that gold clusters interact more strongly with the GC base pair than with isolated guanine. It was found that consequent to the binding of gold nanoclusters a substantial amount of electronic charge was transferred from guanine (or the guanine-cytosine base pair) to t...
