PDBsum entry 168d

DNA-RNA hybrid

PDB id: 168d

Contents

DNA/RNA

Waters ×53

References listed in PDB file

Key reference

Title

Stabilizing effects of the RNA 2'-Substituent: crystal structure of an oligodeoxynucleotide duplex containing 2'-O-Methylated adenosines.

Authors

P.Lubini, W.Zürcher, M.Egli.

Ref.

Chem Biol, 1994, 1, 39-45. [DOI no: 10.1016/1074-5521(94)90039-6]

PubMed id

9383369

Note In the PDB file this reference is annotated as "TO BE PUBLISHED". The citation details given above were identified by an automated search of PubMed on title and author names, giving a perfect match.

Abstract

BACKGROUND: The stability of hybrids of 2'-O-methyl-ribonucleotides with complementary RNA is considerably higher than that of the corresponding DNA.RNA duplexes. The 2'-O-modified ribonucleotides are thus an attractive class of compounds for antisense applications. Understanding how these substituents stabilize the structure of the hybrid duplex may be important in the design of ribonucleotides with novel properties. RESULTS: The crystal structure of a dimer of the self-complementary DNA strand d(GCGT)O2'mer(A)d(TACGC), which has a 2'-O-methylated ribonucleotide incorporated at position 5, was determined at 2.1 A resolution. This strand forms a duplex with an overall A-type conformation; the methyl groups of the two modified adenosines point into the relatively wide minor groove. Both 2'-methoxy groups are hydrogen-bonded to solvent molecules. These results allowed us to build a model of a fully 2'-O-methylated RNA double helix. CONCLUSIONS: Insertion of 2'-O-modified RNA residues into a stretch of DNA can nucleate a local A-type conformation, in part because modification with a bulky residue at this position stabilizes a C3'-endo type sugar pucker. The increased stability of fully 2'-O-methylated RNA may result from hydrophobic interactions between substituents in the minor groove. As the 2'-O-methyl groups are directed into the minor groove, it may be worthwhile to introduce tailor-made 2'-O-substituents into RNA; it might be possible to design groups that both stabilize the hybrid duplexes and carry a nuclease function, further improving the efficacy of these modified RNAs in antisense applications.

Figure 1.
Fig. 1. (a) Sequence and residue numbering of the self- complementry 2'-0-methylated RNA-DNA chimera. DNA residues are bold and 2'-0-methylated RNA residues are

Figure 3.
Fig. 3. (a) Projectio of the base-pair step 02 'mer(A5)*d(T1 6)- d(T6)*02 'mer(Al 5) roughly along the planes of base-pairs, looking into the minor groove. The methoxy groups of the RNA residues adopt an anti arrangement with respect to the ribose moieties, leading to an approximate tram orientation of the

The above figures are reprinted by permission from Cell Press: Chem Biol (1994, 1, 39-45) copyright 1994.