1a8n

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1a8n

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SOLUTION STRUCTURE OF A NA+ CATION STABILIZED DNA QUADRUPLEX CONTAINING G.G.G.G AND G.C.G.C TETRADS FORMED BY G-G-G-C REPEATS OBSERVED IN AAV AND HUMAN CHROMOSOME 19, NMR, 8 STRUCTURES

Overview

We have applied NMR and molecular dynamics computations including, intensity based refinement to define the structure of the, d(G-G-G-C-T4-G-G-G-C) dodecanucleotide in 100 mM NaCl solution. The, G-G-G-C sequence is of interest since it has been found as tandem repeats, in the DNA sequence of human chromosome 19. The same G-G-G-C sequence is, also seen as islands in adeno-associated virus, a human parvovirus, which, is unique amongst eukaryotic DNA viruses in its ability to integrate, site-specifically into a defined region of human chromosome 19. The, d(G-G-G-C-T4-G-G-G-C) sequence forms a quadruplex in Na cation containing, solution through head-to-tail dimerization of two symmetry-related, stem-hairpin loops with adjacent strands antiparallel to each other around, the quadruplex. The connecting T4 loops are of the lateral type, resulting, in a quadruplex structure containing two internal G.G.G.G tetrads flanked, by G.C.G.C tetrads. The G(anti).G(syn).G(anti).G(syn) tetrads are formed, through dimerization associated hydrogen bonding alignments of a pair of, Hoogsteen G(anti).G(syn) mismatch pairs, while the, G(anti).C(anti).G(anti).C(anti) tetrads are formed through dimerization, associated bifurcated hydrogen bonding alignments involving the major, groove edges of a pair of Watson-Crick G.C base-pairs. The quadruplex, contains two distinct narrow and two symmetric wide grooves with extensive, stacking between adjacent tetrad planes. The structure of the quadruplex, contains internal cavities that can potentially accommodate Na cations, positioned between adjacent tetrad planes. Three such Na cations have been, modeled into the structure of the d(G-G-G-C-T4-G-G-G-C) quadruplex., Finally, we speculate on the potential role of quadruplex formation, involving G.G.G.G and G.C.G.C tetrads during the integration of the, adeno-associated parvovirus into its target on human chromosome 19, both, of which involve stretches of G-G-G-C sequence elements.

About this Structure

1A8N is a Protein complex structure of sequences from [1]. Full crystallographic information is available from OCA.

Reference

Solution structure of a Na cation stabilized DNA quadruplex containing G.G.G.G and G.C.G.C tetrads formed by G-G-G-C repeats observed in adeno-associated viral DNA., Kettani A, Bouaziz S, Gorin A, Zhao H, Jones RA, Patel DJ, J Mol Biol. 1998 Sep 25;282(3):619-36. PMID:9737926

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