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6IA0

Human telomeric G-quadruplex with 8-oxo-G substitution in the central G-quartet

Summary for 6IA0
Entry DOI10.2210/pdb6ia0/pdb
NMR InformationBMRB: 34331
DescriptorhTel-oxoG10 (1 entity in total)
Functional Keywordshuman telomere, oxidative stress, g-quadruplex, nmr., dna
Biological sourceHomo sapiens
Total number of polymer chains1
Total formula weight7607.88
Authors
Bielskute, S.,Plavec, J.,Podbevsek, P. (deposition date: 2018-11-26, release date: 2019-01-30, Last modification date: 2024-06-19)
Primary citationBielskute, S.,Plavec, J.,Podbevsek, P.
Impact of Oxidative Lesions on the Human Telomeric G-Quadruplex.
J. Am. Chem. Soc., 141:2594-2603, 2019
Cited by
PubMed Abstract: Telomere attrition is closely associated with cell aging and exposure to reactive oxygen species (ROS). While oxidation products of nucleotides have been studied extensively in the past, the underlying secondary/tertiary structural changes in DNA remain poorly understood. In this work, we systematically probed guanine positions in the human telomeric oligonucleotide sequence (hTel) by substitutions with the major product of ROS, 8-oxo-7,8-dihydroguanine (G), and evaluated the G-quadruplex forming ability of such oligonucleotides. Due to reduced hydrogen-bonding capability caused by G, a loss of G-quadruplex structure was observed for most oligonucleotides containing oxidative lesions. However, some positions in the hTel sequence were found to tolerate substitutions with G. Due to G's preference for the syn conformation, distinct responses were observed when replacing guanines with different glycosidic conformations. Accommodation of G at sites originally in syn or anti in nonsubstituted hTel G-quadruplex requires a minor structural rearrangement or a major conformational shift, respectively. The system responds by retaining or switching to a fold where G is in syn conformation. Most importantly, these G-quadruplex structures are still stable at physiological temperatures and should be considered detrimental in higher-order telomere structures.
PubMed: 30657306
DOI: 10.1021/jacs.8b12748
PDB entries with the same primary citation
Experimental method
SOLUTION NMR
Structure validation

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