1r4d
From Proteopedia
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Solution structure of the chimeric L/D DNA oligonucleotide d(C8metGCGC(L)G(L)CGCG)2
Overview
The structure and thermal stability of a hetero chiral, decaoligodeoxyribonucleotide duplex d(C1m8, G2C3G4C5LG6LC7G8C9G10)d(C11m8G12C13G14C15LG16LC17G18C19G20) (O1) with two, contiguous pairs of enantiomeric 2'-deoxy-L-ribonucleotides, (C5LG6L/C15LG16L) at its centre and an 8-methylguanine at position 2/12, was analysed by circular dichroism, NMR and molecular modelling. O1, resolves in a left-handed helical structure already at low salt, concentration (0.1 M NaCl). The central L2-sugar portion assumes a B*, left-handed conformation (mirror-image of right-handed B-DNA) while its, flanking D4-sugar portions adopt the known Z left-handed conformation. The, resulting Z4-B2*-Z4 structure (left-handed helix) is the reverse of that, of B4-Z2*-B4 (right-handed helix) displayed by the nearly related, decaoligodeoxyribonucleotide d(mC1G2mC3G4C5L G6LmC7G8mC9G10)2, at the same, low salt concentration (0.1 M NaCl). In the same experimental conditions, d(C1m8G2C3G4C5G6C7G8C9G10)2 (O2), the stereoregular version of O1, resolves into a right-handed B-DNA helix. Thus, both the 8-methylguanine, and the enantiomeric step CLpGL at the centre of the molecule are needed, to induce left-handed helicity. Remarkably, in the various heterochiral, decaoligodeoxyribonucleotides so far analysed by us, when the central, CLpGL adopts the B* (respectively Z*) conformation, then the adjacent, steps automatically resolves in the Z (respectively B) conformation. This, allows a good optimisation of the base-base stackings and base-sugar van, der Waals interactions at the ZB*/B*Z (respectively BZ*/Z*B) junctions so, that the Z4-B2*-Z4 (respectively B4-Z2*-B4) helix displays a Tm, (approximately 65 degrees C) that is only 5 degrees C lower than the one, of its homochiral counterpart. Here we anticipate that a large variety of, DNA helices can be generated at low salt concentration by manipulating, internal factors such as sugar configuration, duplex length, nucleotide, composition and base methylation. These helices can constitute powerful, tools for structural and biological investigations, especially as they can, be used in physiological conditions.
About this Structure
1R4D is a Protein complex structure of sequences from [1]. Full crystallographic information is available from OCA.
Reference
L-nucleotides and 8-methylguanine of d(C1m8G2C3G4C5LG6LC7G8C9G10)2 act cooperatively to promote a left-handed helix under physiological salt conditions., Cherrak I, Mauffret O, Santamaria F, Hocquet A, Ghomi M, Rayner B, Fermandjian S, Nucleic Acids Res. 2003 Dec 1;31(23):6986-95. PMID:14627831
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