2M53

G-rich VEGF aptamer with LNA modifications

Summary for 2M53

• Entry DOI: 10.2210/pdb2m53/pdb
• NMR Information: BMRB: 19035
• Descriptor: G-rich VEGF aptamer (1 entity in total)
• Functional Keywords: aptamer, dna, g-quadruplex, locked nucleic acid, vegf
• Biological source: synthetic construct
• Total number of polymer chains: 1
• Total formula weight: 8001.10

Authors

Marusic, M.,Veedu, R.N.,Plavec, J. (deposition date: 2013-02-13, release date: 2013-08-28, Last modification date: 2024-05-15)

Primary citation

Marusic, M.,Veedu, R.N.,Wengel, J.,Plavec, J.
G-rich VEGF aptamer with locked and unlocked nucleic acid modifications exhibits a unique G-quadruplex fold.
Nucleic Acids Res., 41:9524-9536, 2013

PubMed Abstract: The formation of a single G-quadruplex structure adopted by a promising 25 nt G-rich vascular endothelial growth factor aptamer in a K(+) rich environment was facilitated by locked nucleic acid modifications. An unprecedented all parallel-stranded monomeric G-quadruplex with three G-quartet planes exhibits several unique structural features. Five consecutive guanine residues are all involved in G-quartet formation and occupy positions in adjacent DNA strands, which are bridged with a no-residue propeller-type loop. A two-residue D-shaped loop facilitates inclusion of an isolated guanine residue into the vacant spot within the G-quartet. The remaining two G-rich tracts of three residues each adopt parallel orientation and are linked with edgewise and propeller loops. Both 5' with 3 nt and 3' with 4 nt overhangs display well-defined conformations, with latter adopting a basket handle topology. Locked residues contribute to thermal stabilization of the adopted structure and formation of structurally pre-organized intermediates that facilitate folding into a single G-quadruplex. Understanding the impact of chemical modifications on folding, thermal stability and structural polymorphism of G-quadruplexes provides means for the improvement of vascular endothelial growth factor aptamers and advances our insights into driving nucleic acid structure by locking or unlocking the conformation of sugar moieties of nucleotides in general.

PubMed: 23935071
DOI: 10.1093/nar/gkt697

Experimental method

SOLUTION NMR