National Center for
2X2Q: Crystal Structure Of An 'all Locked' Lna Duplex At 1.9 Angstrom Resolution
Nucleic Acids Res. (2010) 38 p.6729-6736
'Locked nucleic acids' (LNAs) are known to introduce enhanced bio- and thermostability into natural nucleic acids rendering them powerful tools for diagnostic and therapeutic applications. We present the 1.9 A X-ray structure of an 'all LNA' duplex containing exclusively modified beta-D-2'-O-4'C-methylene ribofuranose nucleotides. The helix illustrates a new type of nucleic acid geometry that contributes to the understanding of the enhanced thermostability of LNA duplexes. A notable decrease of several local and overall helical parameters like twist, roll and propeller twist influence the structure of the LNA helix and result in a widening of the major groove, a decrease in helical winding and an enlarged helical pitch. A detailed structural comparison to the previously solved RNA crystal structure with the corresponding base pair sequence underlines the differences in conformation. The surrounding water network of the RNA and the LNA helix shows a similar hydration pattern.
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