1d40

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Revision as of 00:18, 25 November 2007

BASE SPECIFIC BINDING OF COPPER(II) TO Z-DNA: THE 1.3-ANGSTROMS SINGLE CRYSTAL STRUCTURE OF D(M5CGUAM5CG) IN THE PRESENCE OF CUCL2

Overview

The single crystal structure of d(m5CGUAm5CG) soaked with copper(II), chloride was solved to atomic (1.3 A) resolution to study the base, specificity of copper binding to double-stranded DNA. In the present, copper(II) chloride-soaked structure, four crystallographically unique, copper(II) complexes were observed bound to five of the six purine bases, in the hexamer duplex. Covalent copper(II) binding occurred at N-7 of all, four guanine bases and at one of the two adenine bases in the DNA duplex., Copper binding was not observed at the position (Ade4) located in an open, solvent channel, whereas the second adenine site (Ade10) shared a complex, with a guanine residue (Gua12) of a neighboring symmetry-related hexamer., The coordination geometries and distribution of these copper(II) complexes, at the guanine bases in the crystal were comparable to the analogous sites, in the isomorphous copper(II) chloride-soaked d(CGCGCG) crystal (Kagawa, T., Geierstanger, B. H., Wang, A. H.-J., and Ho, P.S. (1991) J. Biol., Chem. 266, 20175-20184). Thus, the decreased copper(II) binding affinity, for Ade4 was not an artifact of crystal packing, but is intrinsic to the, chemical properties of this purine base in duplex DNA. This suggests that, the adenine bases in dilute solutions of Z-DNA and more generally other, duplex DNA conformations are not susceptible to copper(II) modification., Thus, preferential copper(II) binding at guanine bases over adenine bases, in double-stranded DNA may explain the observed specificity of, copper(II)-induced oxidative DNA damage near guanine residues (Yamamoto, K., and Kawanishi, S. (1989) J. Biol. Chem. 264, 15435-15440; Sagripanti, J.-L., and Kraemer, K. H. (1989) J. Biol. Chem. 264, 1729-1734). The, sharing of a single copper(II) complex by Ade10 and Gua12 of an adjacent, hexamer suggests that additional and perhaps specific DNA-DNA, interactions, as may be found in the densely packed environment of the, nuclear matrix in the cell, may render N-7 of adenine bases prone to, copper(II) modification.

About this Structure

1D40 is a Protein complex structure of sequences from [1] with CU and CUL as ligands. Full crystallographic information is available from OCA.

Reference

Base-specific binding of copper(II) to Z-DNA. The 1.3-A single crystal structure of d(m5CGUAm5CG) in the presence of CuCl2., Geierstanger BH, Kagawa TF, Chen SL, Quigley GJ, Ho PS, J Biol Chem. 1991 Oct 25;266(30):20185-91. PMID:1939079

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