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• W2161648353 endingPage "12139" @default.
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• W2161648353 abstract "Nucleic acid quadruplexes are composed of guanine quartets stabilized by specific metal ions. X-ray diffraction can provide high-resolution information on the structure and metal binding properties of quadruplexes, but only if they can be crystallized. NMR can provide detailed information on the solution structure of such quadruplexes but little quantitative data concerning the metal binding site. Here we apply extended X-ray absorption fine structure (EXAFS) measurements to characterize the metal ion binding site, in frozen solution, of the unimolecular quadruplex formed by the thrombin binding aptamer, d(G2T2G2TGTG2T2G2) (TBA), in the presence of Pb2+ ions. The Pb LIII -edge X-ray absorption spectrum of this metal−DNA complex is very similar to that we obtain for a Pb2+-stabilized quartet system of known structure constructed from a modified guanine nucleoside (G1). The Fourier transforms of the Pb2+ complexes with both TBA and G1 show a first-shell interaction at about 2.6 Å, and a weaker, broader shell at 3.5−4.0 Å. Quantitative analysis of the EXAFS data reveals the following: (i) very close agreement between interatomic distances at the metal coordination site for the Pb2+−G1 complex determined by EXAFS and by X-ray crystallography; (ii) similarly close agreement between interatomic distances measured by EXAFS for the Pb2+−G1 and Pb2+−TBA complexes. These results provide strong evidence for binding of the Pb2+ ion in the region between the two quartets in the Pb2+−TBA complex, coordinated to the eight surrounding guanine O6 atoms. The specific binding of Pb2+ to DNA examined here may be relevant to the genotoxic effects of this environmentally important heavy metal. Furthermore, these results demonstrate the utility of EXAFS as a method for quantitative characterization of specific metal binding sites in nucleic acids in solution." @default.
• W2161648353 created "2016-06-24" @default.
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• W2161648353 date "2002-09-07" @default.
• W2161648353 modified "2023-10-17" @default.
• W2161648353 title "Pb EXAFS Studies on DNA Quadruplexes: Identification of Metal Ion Binding Site" @default.
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• W2161648353 doi "https://doi.org/10.1021/bi020310p" @default.
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