2KP4

Structure of 2'F-ANA/RNA hybrid duplex

Summary for 2KP4

• Entry DOI: 10.2210/pdb2kp4/pdb
• Descriptor: DNA (5'-D(*(GFL)P*(CFL)P*(TAF)P*(A5L)P*(TAF)P*(A5L)P*(A5L)P*(TAF)P*(GFL)P*(GFL))-3'), RNA (5'-R(*CP*CP*AP*UP*UP*AP*UP*AP*GP*C)-3') (2 entities in total)
• Functional Keywords: 2-deoxy-2-fluoro-d-arabinose, fana, nucleic acid structure, nmr/md/ti, hybrid duplex, dna-rna complex, dna/rna
• Total number of polymer chains: 2
• Total formula weight: 6385.85

Authors

Gonzalez, C.,Martin-Pintado, N.,Watts, J.,Gomez-Pinto, I.,Dhama, M.,Orozco, M.,Schwartzentruber, J.,Portella, G. (deposition date: 2009-10-06, release date: 2010-02-09, Last modification date: 2024-05-22)

Primary citation

Watts, J.K.,Martin-Pintado, N.,Gomez-Pinto, I.,Schwartzentruber, J.,Portella, G.,Orozco, M.,Gonzalez, C.,Damha, M.J.
Differential stability of 2'F-ANA*RNA and ANA*RNA hybrid duplexes: roles of structure, pseudohydrogen bonding, hydration, ion uptake and flexibility.
Nucleic Acids Res., 38:2498-2511, 2010

PubMed Abstract: Hybrids of RNA with arabinonucleic acids 2'F-ANA and ANA have very similar structures but strikingly different thermal stabilities. We now present a thorough study combining NMR and other biophysical methods together with state-of-the-art theoretical calculations on a fully modified 10-mer hybrid duplex. Comparison between the solution structure of 2'F-ANA*RNA and ANA*RNA hybrids indicates that the increased binding affinity of 2'F-ANA is related to several subtle differences, most importantly a favorable pseudohydrogen bond (2'F-purine H8) which contrasts with unfavorable 2'-OH-nucleobase steric interactions in the case of ANA. While both 2'F-ANA and ANA strands maintained conformations in the southern/eastern sugar pucker range, the 2'F-ANA strand's structure was more compatible with the A-like structure of a hybrid duplex. No dramatic differences are found in terms of relative hydration for the two hybrids, but the ANA*RNA duplex showed lower uptake of counterions than its 2'F-ANA*RNA counterpart. Finally, while the two hybrid duplexes are of similar rigidities, 2'F-ANA single strands may be more suitably preorganized for duplex formation. Thus the dramatically increased stability of 2'F-ANA*RNA and ANA*RNA duplexes is caused by differences in at least four areas, of which structure and pseudohydrogen bonding are the most important.

PubMed: 20071751
DOI: 10.1093/nar/gkp1225

Experimental method

SOLUTION NMR