The Experts below are selected from a list of 309 Experts worldwide ranked by ideXlab platform
Gustavo Portalone - One of the best experts on this subject based on the ideXlab platform.
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Solid-phase molecular recognition of Cytosine based on proton-transfer reaction. Part II. supramolecular architecture in the cocrystals of Cytosine and its 5-Fluoroderivative with 5-Nitrouracil
Chemistry Central Journal, 2011Co-Authors: Gustavo PortaloneAbstract:Background Cytosine is a biologically important compound owing to its natural occurrence as a component of nucleic acids. Cytosine plays a crucial role in DNA/RNA base pairing, through several hydrogen-bonding patterns, and controls the essential features of life as it is involved in genetic codon of 17 amino acids. The molecular recognition among Cytosines, and the molecular heterosynthons of molecular salts fabricated through proton-transfer reactions, might be used to investigate the theoretical sites of Cytosine-specific DNA-binding proteins and the design for molecular imprint. Results Reaction of Cytosine (Cyt) and 5-fluoroCytosine (5Fcyt) with 5-nitrouracil (Nit) in aqueous solution yielded two new products, which have been characterized by single-crystal X-ray diffraction. The products include a dihydrated molecular salt (CytNit) having both ionic and neutral hydrogen-bonded species, and a dihydrated cocrystal of neutral species (5FcytNit). In CytNit a protonated and an unprotonated Cytosine form a triply hydrogen-bonded aggregate in a self-recognition ion-pair complex, and this dimer is then hydrogen bonded to one neutral and one anionic 5-nitrouracil molecule. In 5FcytNit the two neutral nucleobase derivatives are hydrogen bonded in pairs. In both structures conventional N-H^...O, O-H^...O, N-H^+...N and N-H^...N^- intermolecular interactions are most significant in the structural assembly. Conclusion The supramolecular structure of the molecular adducts formed by Cytosine and 5-fluoroCytosine with 5-nitrouracil, CytNit and 5FcytNit, respectively, have been investigated in detail. CytNit and 5FcytNit exhibit widely differing hydrogen-bonding patterns, though both possess layered structures. The crystal structures of CytNit (D p k_a = -0.7, molecular salt) and 5FcytNit (D p k_a = -2.0, cocrystal) confirm that, at the present level of knowledge about the nature of proton-transfer process, there is not a strict correlation between the D p k_a values and the proton transfer, in that the acid/base p k_a strength is not a definite guide to predict the location of H atoms in the solid state. Eventually, the absence in 5FcytNit of hydrogen bonds involving fluorine is in agreement with findings that covalently bound fluorine hardly ever acts as acceptor for available Brønsted acidic sites in the presence of competing heteroatom acceptors.
Patricia L Foster - One of the best experts on this subject based on the ideXlab platform.
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strand biased Cytosine deamination at the replication fork causes Cytosine to thymine mutations in escherichia coli
Proceedings of the National Academy of Sciences of the United States of America, 2016Co-Authors: Ashok S Bhagwat, Jesse P Townes, Haixu Tang, Patricia L FosterAbstract:The rate of Cytosine deamination is much higher in single-stranded DNA (ssDNA) than in double-stranded DNA, and copying the resulting uracils causes C to T mutations. To study this phenomenon, the catalytic domain of APOBEC3G (A3G-CTD), an ssDNA-specific Cytosine deaminase, was expressed in an Escherichia coli strain defective in uracil repair (ung mutant), and the mutations that accumulated over thousands of generations were determined by whole-genome sequencing. C:G to T:A transitions dominated, with significantly more Cytosines mutated to thymine in the lagging-strand template (LGST) than in the leading-strand template (LDST). This strand bias was present in both repair-defective and repair-proficient cells and was strongest and highly significant in cells expressing A3G-CTD. These results show that the LGST is accessible to cellular Cytosine deaminating agents, explains the well-known GC skew in microbial genomes, and suggests the APOBEC3 family of mutators may target the LGST in the human genome.
M T Rodgers - One of the best experts on this subject based on the ideXlab platform.
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base pairing energies of proton bound heterodimers of Cytosine and modified Cytosines implications for the stability of dna i motif conformations
Journal of the American Chemical Society, 2014Co-Authors: Bo Yang, M T RodgersAbstract:The DNA i-motif conformation was discovered in (CCG)•(CGG)n trinucleotide repeats, which are associated with fragile X syndrome, the most widespread inherited cause of mental retardation in humans. The DNA i-motif is a four-stranded structure whose strands are held together by proton-bound dimers of Cytosine (C+•C). The stronger base-pairing interactions in C+•C proton-bound dimers as compared to Watson–Crick G•C base pairs are the major forces responsible for stabilization of i-motif conformations. Methylation of Cytosine results in silencing of the FMR1 gene and causes fragile X syndrome. However, the influence of methylation or other modifications such as halogenation of Cytosine on the base-pairing energies (BPEs) in the i-motif remains elusive. To address this, proton-bound heterodimers of Cytosine and 5-methylCytosine, 5-fluoroCytosine, 5-bromoCytosine, and 5-iodoCytosine are probed in detail. Experimentally, the BPEs of proton-bound heterodimers of Cytosine and modified Cytosines are determined usi...
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Base-pairing energies of proton-bound homodimers determined by guided ion beam tandem mass spectrometry: application to Cytosine and 5-substituted Cytosines.
Analytical Chemistry, 2013Co-Authors: Bo Yang, R R Wu, M T RodgersAbstract:Base-pairing interactions in proton-bound dimers of Cytosine (C+·C) are the major forces responsible for stabilization of DNA i-motif conformations. Permethylation of Cytosine in extended (CCG)·(CGG)n trinucleotide repeats has been shown to cause fragile-X syndrome, the most widespread inherited cause of mental retardation in humans. Oligonucleotides containing 5-bromo- or 5-fluoroCytosine can bind to proteins that selectively bind methylated DNA, suggesting that halogenated Cytosine damage products can potentially mimic methylation signals. However, the influence of methylation or halogenation on the base-pairing energies (BPEs) of proton-bound dimers of Cytosine and their impact on the stability of DNA i-motif conformations is presently unknown. To address this, proton-bound homodimers of Cytosine and 5-methyl-, 5-fluoro-, 5-bromo-, and 5-iodoCytosine are investigated in detail both experimentally and theoretically. The BPEs of proton-bound homodimers of Cytosine and the modified Cytosines are measured ...
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irmpd action spectroscopy of alkali metal cation Cytosine complexes effects of alkali metal cation size on gas phase conformation
Journal of the American Society for Mass Spectrometry, 2013Co-Authors: Bo Yang, Nicolas C. Polfer, R R Wu, Giel Berden, Jos Oomens, M T RodgersAbstract:The gas-phase structures of alkali metal cation-Cytosine complexes generated by electrospray ionization are probed via infrared multiple photon dissociation (IRMPD) action spectroscopy and theoretical calculations. IRMPD action spectra of five alkali metal cation–Cytosine complexes exhibit both similar and distinctive spectral features over the range of ~1000–1900 cm-1. The IRMPD spectra of the Li+(Cytosine), Na+(Cytosine), and K+(Cytosine) complexes are relatively simple but exhibit changes in the shape and shifts in the positions of several bands that correlate with the size of the alkali metal cation. The IRMPD spectra of the Rb+(Cytosine) and Cs+(Cytosine) complexes are much richer as distinctive new IR bands are observed, and the positions of several bands continue to shift in relation to the size of the metal cation. The measured IRMPD spectra are compared to linear IR spectra of stable low-energy tautomeric conformations calculated at the B3LYP/def2-TZVPPD level of theory to identify the conformations accessed in the experiments. These comparisons suggest that the evolution in the features in the IRMPD action spectra with the size of the metal cation, and the appearance of new bands for the larger metal cations, are the result of the variations in the intensities at which these complexes can be generated and the strength of the alkali metal cation-Cytosine binding interaction, not the presence of multiple tautomeric conformations. Only a single tautomeric conformation is accessed for all five alkali metal cation–Cytosine complexes, where the alkali metal cation binds to the O2 and N3 atoms of the canonical amino-oxo tautomer of Cytosine, M+(C1).
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IRMPD Action Spectroscopy of Alkali Metal Cation–Cytosine Complexes: Effects of Alkali Metal Cation Size on Gas Phase Conformation
Journal of the American Society for Mass Spectrometry, 2013Co-Authors: Bo Yang, Nicolas C. Polfer, R R Wu, Giel Berden, Jos Oomens, M T RodgersAbstract:The gas-phase structures of alkali metal cation-Cytosine complexes generated by electrospray ionization are probed via infrared multiple photon dissociation (IRMPD) action spectroscopy and theoretical calculations. IRMPD action spectra of five alkali metal cation–Cytosine complexes exhibit both similar and distinctive spectral features over the range of ~1000–1900 cm-1. The IRMPD spectra of the Li+(Cytosine), Na+(Cytosine), and K+(Cytosine) complexes are relatively simple but exhibit changes in the shape and shifts in the positions of several bands that correlate with the size of the alkali metal cation. The IRMPD spectra of the Rb+(Cytosine) and Cs+(Cytosine) complexes are much richer as distinctive new IR bands are observed, and the positions of several bands continue to shift in relation to the size of the metal cation. The measured IRMPD spectra are compared to linear IR spectra of stable low-energy tautomeric conformations calculated at the B3LYP/def2-TZVPPD level of theory to identify the conformations accessed in the experiments. These comparisons suggest that the evolution in the features in the IRMPD action spectra with the size of the metal cation, and the appearance of new bands for the larger metal cations, are the result of the variations in the intensities at which these complexes can be generated and the strength of the alkali metal cation-Cytosine binding interaction, not the presence of multiple tautomeric conformations. Only a single tautomeric conformation is accessed for all five alkali metal cation–Cytosine complexes, where the alkali metal cation binds to the O2 and N3 atoms of the canonical amino-oxo tautomer of Cytosine, M+(C1).
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tautomerization in the formation and collision induced dissociation of alkali metal cation Cytosine complexes
Physical Chemistry Chemical Physics, 2012Co-Authors: Zhibo Yang, M T RodgersAbstract:Noncovalent interactions between alkali metal cations and the various low-energy tautomeric forms of Cytosine are investigated both experimentally and theoretically. Threshold collision-induced dissociation (CID) of M+(Cytosine) complexes with Xe is studied using guided ion beam tandem mass spectrometry, where M+ = Li+, Na+, and K+. In all cases, the only dissociation pathway observed corresponds to endothermic loss of the intact Cytosine molecule. The cross-section thresholds are interpreted to yield 0 and 298 K bond dissociation energies (BDEs) for the M+(Cytosine) complexes after accounting for the effects of multiple ion-neutral collisions, the kinetic and internal energy distributions of the reactants, and dissociation lifetimes. Ab initio calculations are performed at the MP2(full)/6-31G* level of theory to determine the structures of the neutral Cytosine tautomers, the M+(Cytosine) complexes, and the TSs for unimolecular tautomerization. The molecular parameters derived from these structures are employed for the calculation of the unimolecular rates for tautomerization and the thermochemical analysis of the experimental data. Theoretical BDEs of the various M+(Cytosine) complexes and the energy barriers for the unimolecular tautomerization of these complexes are determined at MP2(full)/6-311+G(2d,2p) level of theory using the MP2(full)/6-31G* optimized geometries. In addition, BDEs for the Li+(Cytosine) complexes are also determined at the G3 level of theory. Based upon the tautomeric mixture generated upon thermal vaporization of Cytosine, calculated M+–Cytosine BDEs and barriers to tautomerization for the low-energy tautomeric forms of M+(Cytosine), and measured thresholds for CID of M+(Cytosine) complexes, we conclude that tautomerization occurs during both complex formation and CID.
Zefeng Wang - One of the best experts on this subject based on the ideXlab platform.
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specific and modular binding code for Cytosine recognition in pumilio fbf puf rna binding domains
Journal of Biological Chemistry, 2011Co-Authors: Shuyun Dong, Yang Wang, Caleb Cassidyamstutz, Gang Lu, Rebecca L Bigler, Mark R Jezyk, Chunhua Li, Traci Tanaka M Hall, Zefeng WangAbstract:Pumilio/fem-3 mRNA-binding factor (PUF) proteins possess a recognition code for bases A, U, and G, allowing designed RNA sequence specificity of their modular Pumilio (PUM) repeats. However, recognition side chains in a PUM repeat for Cytosine are unknown. Here we report identification of a Cytosine-recognition code by screening random amino acid combinations at conserved RNA recognition positions using a yeast three-hybrid system. This C-recognition code is specific and modular as specificity can be transferred to different positions in the RNA recognition sequence. A crystal structure of a modified PUF domain reveals specific contacts between an arginine side chain and the Cytosine base. We applied the C-recognition code to design PUF domains that recognize targets with multiple Cytosines and to generate engineered splicing factors that modulate alternative splicing. Finally, we identified a divergent yeast PUF protein, Nop9p, that may recognize natural target RNAs with Cytosine. This work deepens our understanding of natural PUF protein target recognition and expands the ability to engineer PUF domains to recognize any RNA sequence.
Michaela Frye - One of the best experts on this subject based on the ideXlab platform.
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nsun2 mediated Cytosine 5 methylation of vault noncoding rna determines its processing into regulatory small rnas
Cell Reports, 2013Co-Authors: Shobbir Hussain, Abdulrahim A Sajini, Sandra Blanco, Sabine Dietmann, Patrick Lombard, Yoichiro Sugimoto, Maike Paramor, Joseph G Gleeson, Duncan T Odom, Michaela FryeAbstract:Autosomal-recessive loss of the NSUN2 gene has been identified as a causative link to intellectual disability disorders in humans. NSun2 is an RNA methyltransferase modifying Cytosine-5 in transfer RNAs (tRNAs), yet the identification of Cytosine methylation in other RNA species has been hampered by the lack of sensitive and reliable molecular techniques. Here, we describe miCLIP as an additional approach for identifying RNA methylation sites in transcriptomes. miCLIP is a customized version of the individual-nucleotide-resolution crosslinking and immunoprecipitation (iCLIP) method. We confirm site-specific methylation in tRNAs and additional messenger and noncoding RNAs (ncRNAs). Among these, vault ncRNAs contained six NSun2-methylated Cytosines, three of which were confirmed by RNA bisulfite sequencing. Using patient cells lacking the NSun2 protein, we further show that loss of Cytosine-5 methylation in vault RNAs causes aberrant processing into Argonaute-associated small RNA fragments that can function as microRNAs. Thus, impaired processing of vault ncRNA may contribute to the etiology of NSun2-deficiency human disorders.
