Solution structure of 2′,5′ d(G4C4): Relevance to topological restrictions and nature's choice of phosphodiester links

Bernard J. Premraj, Swaminathan Raja, Neel S. Bhavesh, Ke Shi, Ramakrishna V. Hosur, Muttaiya Sundaralingam, Narayanarao Yathindra

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

The NMR structure of 2′,5′ d(GGGGCCCC) was determined to gain insights into the structural differences between 2′,5′- and 3′,5′-linked DNA duplexes that may be relevant in elucidating nature's choice of sugar-phosphate links to encode genetic information. The oligomer assumes a duplex with extended nucleotide repeats formed out of mostly N-type sugar puckers. With the exception of the 5′-terminal guanine that assumes the syn glycosyl conformation, all other bases prefer the anti glycosyl conformation. Base pairs in the duplex exhibit slide (-1.96 Å) and intermediate values for X-displacement (-3.23 Å), as in ADNA, while their inclination to the helical axis is not prominent. Major and minor grooves display features intermediate to A and BDNA. The duplex structure of iso d(GGGGCCCC) may therefore be best characterized as a hybrid of A and BDNA. Importantly, the results confirm that even 3̊ deoxy 2̊,5̊ DNA supports duplex formation only in the presence of distinct slide (≥ -1.6 Å) and X-displacement (≥ -2.5 Å) for base pairs, and hence does not favor an ideal BDNA topology characterized by their near-zero values. Such restrictions on base pair movements in 2′,5′ DNA, which are clearly absent in 3′,5′ DNA, are expected to impose constraints on its ability for deformability of the kind observed in DNA during its compaction and interaction with proteins. It is therefore conceivable that selection pressure relating to the optimization of topological features might have been a factor in the rejection of 2′,5′ links in preference to 3′,5′ links.

Original languageEnglish (US)
Pages (from-to)2956-2966
Number of pages11
JournalEuropean Journal of Biochemistry
Volume271
Issue number14
DOIs
StatePublished - Jul 1 2004

Keywords

  • AB hybrid structure
  • Evolution of 3′,5′ vs. 2′,5′ links in nucleic acids
  • Restrained base pair movements
  • Structure of 2′,5′ DNA
  • Topological restrictions in 2′,5′ DNA

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