1A8W

A K+ CATION-INDUCED CONFORMATIONAL SWITCH WITHIN A LOOP SPANNING SEGMENT OF A DNA QUADRUPLEX CONTAINING G-G-G-C REPEATS, NMR, 8 STRUCTURES

Summary for 1A8W

• Entry DOI: 10.2210/pdb1a8w/pdb
• Descriptor: DNA QUADRUPLEX CONTAINING GGGG TETRADS AND GC WATSON-CRICK BASE PAIRS (1 entity in total)
• Functional Keywords: cation dependent conformational transitions, k+ cation coordination sites, k+ cation encapsulation within a hairpin loop, dna quadruplexes targeted to hiv integrase, deoxyribonucleic acid, g-g-g-c repeat-containing dna quadruplexes, monovalent, dna
• Total number of polymer chains: 2
• Total formula weight: 7450.82

Authors

Bouaziz, S.,Kettani, A.,Patel, D.J. (deposition date: 1998-03-28, release date: 1998-10-14, Last modification date: 2024-05-22)

Primary citation

Bouaziz, S.,Kettani, A.,Patel, D.J.
A K cation-induced conformational switch within a loop spanning segment of a DNA quadruplex containing G-G-G-C repeats.
J.Mol.Biol., 282:637-652, 1998

PubMed Abstract: We have identified a unique structural transition (in slow exchange on the NMR time scale) in the tertiary fold of the d(G-G-G-C-T4-G-G-G-C) quadruplex on proceeding from Na+ to K+ as counterion in aqueous solution. Both monovalent cation-dependent conformations exhibit certain common structural features, which include head-to-tail dimerization of two symmetry-related stem-hairpin loops, adjacent strands which are antiparallel to each other and adjacent stacked G(syn).G(anti). G(syn).G(anti) tetrads in the central core of the quadruplexes. The Na and K cation stabilized structures of the d(G-G-G-C-T4-G-G-G-C) quadruplexes differ in the conformations of the T-T-T-T loops, the relative alignment of G.C base-pairs positioned opposite each other through their major groove edges and potentially in the number of monovalent cation binding sites. We have identified potential K cation binding cavities within the symmetry-related T-T-T-G segments, suggesting the potential for two additional monovalent cation binding sites in the K cation-stabilized quadruplex relative to its Na cation-stabilized counterpart. Modeling studies suggest that the major groove edges of guanine residues in Watson-Crick G.C base-pairs could potentially be bridged by coordinated K cations in the d(G-G-G-C-T4-G-G-G-C) quadruplex in KCl solution in contrast to formation of G.C.G.C tetrads for the corresponding quadruplex in NaCl solution. Our results defining the molecular basis of a Na to K cation-dependent conformational switch in the loop spanning segment of the d(G-G-G-C-T4-G-G-G-C) quadruplex may have relevance to recent observations that specific K cation coordinated loop conformations within quadruplexes exhibit inhibitory activity against HIV integrase.

PubMed: 9737927
DOI: 10.1006/jmbi.1998.2031

Experimental method

SOLUTION NMR