5MCR

Quadruplex with flipped tetrad formed by an artificial sequence

Summary for 5MCR

• Entry DOI: 10.2210/pdb5mcr/pdb
• NMR Information: BMRB: 34063
• Descriptor: Artificial quadruplex with propeller, diagonal and lateral loop (1 entity in total)
• Functional Keywords: g-quadruplex, dna
• Biological source: synthetic construct
• Total number of polymer chains: 1
• Total formula weight: 6946.48

Authors

Dickerhoff, J.,Haase, L.,Langel, W.,Weisz, K. (deposition date: 2016-11-10, release date: 2017-04-19, Last modification date: 2024-05-15)

Primary citation

Dickerhoff, J.,Haase, L.,Langel, W.,Weisz, K.
Tracing Effects of Fluorine Substitutions on G-Quadruplex Conformational Changes.
ACS Chem. Biol., 12:1308-1315, 2017

PubMed Abstract: A human telomere sequence that folds into an intramolecular (3 + 1)-hybrid G-quadruplex was modified by the incorporation of 2'-fluoro-2'-deoxyriboguanosines (G) into syn positions of its outer tetrad. A circular dichroism and NMR spectral analysis reveals a nearly quantitative switch of the G-tetrad polarity with concerted syn↔anti transitions of all four G residues. These observations follow findings on a G-substituted (3 + 1)-hybrid quadruplex with a different fold, suggesting a more general propensity of hybrid-type quadruplexes to undergo a tetrad polarity reversal. Two out of the three G analogs in both modified quadruplexes adopt an S-type sugar pucker, challenging a sole contribution of N-type sugars in enforcing an anti glycosidic torsion angle associated with the tetrad flip. NMR restrained three-dimensional structures of the two substituted quadruplexes reveal a largely conserved overall fold but significant rearrangements of the overhang and loop nucleotides capping the flipped tetrad. Sugar pucker preferences of the G analogs may be rationalized by different orientations of the fluorine atom and its resistance to be positioned within the narrow groove with its highly negative electrostatic potential and spine of water molecules.

PubMed: 28318229
DOI: 10.1021/acschembio.6b01096

Experimental method

SOLUTION NMR