2MWZ

Xanthine and 8-oxoguanine in G-quadruplexes: formation of a G G X O tetrad

Summary for 2MWZ

• Entry DOI: 10.2210/pdb2mwz/pdb
• Related: 2GKU
• NMR Information: BMRB: 25378
• Descriptor: DNA (5'-D(*TP*TP*GP*GP*GP*TP*TP*AP*(8OG)P*GP*GP*TP*TP*AP*GP*GP*(3ZO)P*TP*TP*AP*GP*GP*GP*A)-3') (1 entity in total)
• Functional Keywords: xanthosine, dna
• Total number of polymer chains: 1
• Total formula weight: 7608.87

Authors

Cheong, V.V.,Heddi, B.,Lech, C.J.,Phan, A.T. (deposition date: 2014-12-04, release date: 2015-10-14, Last modification date: 2024-05-15)

Primary citation

Cheong, V.V.,Heddi, B.,Lech, C.J.,Phan, A.T.
Xanthine and 8-oxoguanine in G-quadruplexes: formation of a GGXO tetrad.
Nucleic Acids Res., 43:10506-10514, 2015

PubMed Abstract: G-quadruplexes are four-stranded structures built from stacked G-tetrads (G·G·G·G), which are planar cyclical assemblies of four guanine bases interacting through Hoogsteen hydrogen bonds. A G-quadruplex containing a single guanine analog substitution, such as 8-oxoguanine (O) or xanthine (X), would suffer from a loss of a Hoogsteen hydrogen bond within a G-tetrad and/or potential steric hindrance. We show that a proper arrangement of O and X bases can reestablish the hydrogen-bond pattern within a G·G·X·O tetrad. Rational incorporation of G·G·X·O tetrads in a (3+1) G-quadruplex demonstrated a similar folding topology and thermal stability to that of the unmodified G-quadruplex. pH titration conducted on X·O-modified G-quadruplexes indicated a protonation-deprotonation equilibrium of X with a pKa ∼6.7. The solution structure of a G-quadruplex containing a G·G·X·O tetrad was determined, displaying the same folding topology in both the protonated and deprotonated states. A G-quadruplex containing a deprotonated X·O pair was shown to exhibit a more electronegative groove compared to that of the unmodified one. These differences are likely to manifest in the electronic properties of G-quadruplexes and may have important implications for drug targeting and DNA-protein interactions.

PubMed: 26400177
DOI: 10.1093/nar/gkv826

Experimental method

SOLUTION NMR