Conformational flexibility in DNA duplexes containing single G.G mismatches - PubMed (original) (raw)
Conformational flexibility in DNA duplexes containing single G.G mismatches
A N Lane et al. Eur J Biochem. 1995.
Free article
Abstract
Purine-purine mismatches can base-pair in a variety of configurations depending on solution conditions. The G.G mismatch, which also occurs in the G-quartet structure, has been shown by both x-ray crystallography and NMR to adopt G(anti).G(syn) mispairs, with very different hydrogen bonding patterns [Skelly, J., Edwards, K., Jenkins, T. C. & Neidle, S. (1993) Proc. Natl Acad. Sci. USA 90, 804-808; Cognet, J. A. H., Gabarro-Arpa, J., Le Bret, M., van der Marel, G. A. van Boom, J. H. & Fazakerley, G. V. (1991) Nucleic Acids. Res. 19, 6771-6779] while we have recently suggested the presence of weakly hydrogen-bonded G(anti).G(anti) pairs in solution [Borden, K. L. B., Jenkins, T. C., Skelly, J. V., Brown, T. & Lane, A. N. (1992) Biochemistry 31, 5411-5422]. Spectral overlap and additional exchange processes have made detailed structural analysis difficult in these mismatched oligomers. We have used NMR to characterise the conformations of four duplexes containing single G.G mismatches, including a nonamer d(CATCGGATG), two undecamers d(GCATTGAATGC) and d(CATGTGACGTG) that can each form a self-complementary duplex with a single G.G mispair in the centre, and the non-self-complementary d(GTAACGACATG).d(CATGTGGTTAC). The three self-complementary duplexes have a single set of NMR resonances, and all four duplexes show evidence of conformational exchange at the mismatch site. The N1H resonances of the mismatched G residues each integrate to two protons, ruling out the enol tautomer. They resonate between 10.5-10.7 ppm, far upfield of the Watson-Crick hydrogen-bonded GN1H and exchange readily with water protons. Intraresidue GH8-H1' NOE intensities are two-threefold larger for the mismatched G residues than in G.C base pairs, indicating the presence of syn conformations. NOE time courses for the self-complementary duplexes were consistent with an equimolar mixture of G(syn).G(anti) and G (anti).G(syn) states. By symmetry, these states must be interconverting at a rate that is fast on the chemical shift timescale. In the non-self-complementary undecamer, the NOE data indicated that the distinguishable mismatched G residues also spend a significant, but different, fraction of the time in both the syn and anti conformations. The rate constant for the syn/anti transition in the non-self-complementary undecamer was determined as approximately 14,000 s-1 at 303 K from rotating frame T1 measurements, and the apparent frequency difference was > 250 Hz. Calculations based on NOEs and coupling constants showed that the duplexes are overall in the B form.(ABSTRACT TRUNCATED AT 250 WORDS)
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