146d

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SOLUTION STRUCTURE OF THE MITHRAMYCIN DIMER-DNA COMPLEX

Overview

We have characterized the NMR parameters for the complexes formed by the, Mg(2+)-coordinated mithramycin dimer with self-complementary, d(T-G-G-C-C-A) and d(T-C-G-C-G-A) duplexes. The solution structure of the, latter complex has been determined using a combined NMR-molecular dynamics, study including relaxation matrix refinement. The Mg(2+)-coordinated, mithramycin dimer-d(T-C-G-C-G-A) complex exhibits a 2-fold center of, symmetry with the divalent cation coordinated aglycons positioned opposite, the central (G3-C4).(G3-C4) segment such that the aglycon C8 hydroxyl, oxygens form symmetrical sequence-specific hydrogen bonds to guanine amino, protons in the complex. The C-D-E trisaccharide segments of each monomer, in the mithramycin dimer adopt extended conformations, are positioned, inside the minor groove, and are directed toward either end of the duplex., The C-D saccharide component of one monomer and the aglycon of the other, monomer in the mithramycin dimer share a widened minor groove with the, hydrophobic edges of the C and D sugars interacting with individual, strands of the duplex. The E-sugar ring is positioned in the floor of the, minor groove, and its hydroxyl-bearing face interacts with both strands of, the duplex through hydrogen-bonding and hydrophobic intermolecular, interactions. The A-B disaccharide and the hydrophilic side chain form, intermolecular contacts with the sugar-phosphate backbone in the complex., The antiparallel alignment of divalent cation coordinated monomers in the, mithramycin dimer results in the two outwardly directed C-D-E, trisaccharide segments generating a right-handed continuous hexasaccharide, domain that spans six base pairs in the minor groove of the duplex. The, solution structure of the mithramycin dimer-DNA complex reported in this, study and the solution structure of the chromomycin dimer-DNA complex, reported previously [Gao, X., Mirau, P., & Patel, D. J. (1992) J. Mol., Biol. 223, 259-279] show global similarities, as well as local differences, that are of interest. All four nucleotides in the tetranucleotide segment, of the duplex centered about the sequence-specific (G-C).(G-C) step adopt, A-DNA sugar puckers and glycosidic torsion angles in the chromomycin, dimer-DNA complex, while only the central cytidine adopts an A-DNA sugar, pucker and glycosidic torsion angle in the mithramycin dimer-DNA, complex.(ABSTRACT TRUNCATED AT 400 WORDS)

About this Structure

146D is a Protein complex structure of sequences from [1] with MG, CRH and MDA as ligands. Full crystallographic information is available from OCA.

Reference

Solution structure of the mithramycin dimer-DNA complex., Sastry M, Patel DJ, Biochemistry. 1993 Jul 6;32(26):6588-604. PMID:8329387

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