1NP9

Structure of the parallel-stranded DNA quadruplex d(TTAGGGA)4 containing the human telomeric repeat

Summary for 1NP9

• Entry DOI: 10.2210/pdb1np9/pdb
• NMR Information: BMRB: 5737
• Descriptor: 5'-D(*TP*TP*AP*GP*GP*GP*T)-3' (1 entity in total)
• Functional Keywords: parallel-stranded quadruplex dna, ttagggt repeat, a-tetrad, dna
• Total number of polymer chains: 4
• Total formula weight: 8673.78

Authors

Gavathiotis, E.,Searle, M.S. (deposition date: 2003-01-17, release date: 2003-09-16, Last modification date: 2024-05-22)

Primary citation

Gavathiotis, E.,Searle, M.S.
Structure of the parallel-stranded DNA quadruplex d(TTAGGGT)4 containing the human telomeric repeat: evidence for A-tetrad formation from NMR and molecular dynamics simulations.
ORG.BIOMOL.CHEM., 1:1650-1656, 2003

PubMed Abstract: The structure of the intermolecular DNA quadruplex d(TTAGGGT)4, based on the human telomeric DNA sequence d(TTAGGG), has been determined in solution by NMR and restrained molecular dynamics simultations. The core GGG region forms a highly stable quadruplex with G-tetrads likely stabilised by K+ ions bound between tetrad plains. However, we have focused on the conformation of the adenines which differ considerably in base alignment, stability and dynamics from those in previously reported structures of d(AGGGT)4 and d(TAGGGT)4. We show unambiguously that the adenines of d(TTAGGGT)4 are involved in the formation of a relatively stable A-tetrad with well-defined glycosidic torsion angles (anti), hydrogen bonding network (adenine 6-NH2-adenine N1) defined by interbase NOEs, and base stacking interactions with the neighbouring G-tetrad. All of these structural features are apparent from NOE data involving both exchangeable and non-exchangeable protons. Thus, context-dependent effects appear to play some role in dictating preferred conformation, stability and dynamics. The structure of d(TTAGGGT)4 provides us with a model system for exploiting in the design of novel telomerase inhibitors that bind to and stabilise G-quadruplex structures.

PubMed: 12926351
DOI: 10.1039/b300845m

Experimental method

SOLUTION NMR