4L0A: X-ray Structure Of An All Lna Quadruplex

Locked nucleic acids (LNAs) are formed by bicyclic ribonucleotides where the O2' and C4' atoms are linked through a methylene bridge and the sugar is blocked in a 3'-endo conformation. They represent a promising tool for therapeutic and diagnostic applications and are characterized by higher thermal stability and nuclease resistance with respect to their natural counterparts. However, structural descriptions of LNA-containing quadruplexes are rather limited, since few NMR models have been reported in the literature. Here, the first crystallographically derived model of an all-LNA-substituted quadruplex-forming sequence 5'-TGGGT-3' is presented refined at 1.7 A resolution. This high-resolution crystallographic analysis reveals a regular parallel G-quadruplex arrangement terminating in a well defined thymine tetrad at the 3'-end. The detailed picture of the hydration pattern reveals LNA-specific features in the solvent distribution. Interestingly, two closely packed quadruplexes are present in the asymmetric unit. They face one another with their 3'-ends giving rise to a compact higher-order structure. This new assembly suggests a possible way in which sequential quadruplexes can be disposed in the crowded cell environment. Furthermore, as the formation of ordered structures by molecular self-assembly is an effective strategy to obtain nanostructures, this study could open the way to the design of a new class of LNA-based building blocks for nanotechnology.
PDB ID: 4L0ADownload
MMDB ID: 118004
PDB Deposition Date: 2013/5/31
Updated in MMDB: 2014/03
Experimental Method:
x-ray diffraction
Resolution: 1.7  Å
Biological Unit for 4L0A: octameric; determined by author
Molecular Components in 4L0A
Label Count Molecule
Nucleotide(1 molecule)
Dna/rna (5'-r(*(tln)p*(lcg)p*(lcg)p*(lcg)p*(tln))-3')
Molecule annotation
Chemicals (5 molecules)
* Click molecule labels to explore molecular sequence information.

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