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1fix

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Image:1fix.jpg

1fix, resolution 2.300Å

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THE STRUCTURE OF AN RNA/DNA HYBRID: A SUBSTRATE OF THE RIBONUCLEASE ACTIVITY OF HIV-1 REVERSE TRANSCRIPTASE

Overview

The structure of a complementary hybrid duplex of RNA and DNA has been, determined by X-ray crystallography. A ten residue DNA oligonucleotide of, sequence 5'-G-G-C-G-C-C-C-G-A-A-3' was annealed to complementary RNA, (5'-u-u-c-g-g-g-c-g-c-c-3') and crystallized, producing tetragonal, crystals that diffract to 2.3 A resolution. The hybrid adopts a geometry, that is neither strictly A nor B-form, rather the helix possesses, qualities of both, reminiscent of spectroscopic descriptions of a hybrid, conformation, or H-form. All of the ribonucleotides maintain the C3'-endo, conformation seen in A-form, while both C3'-endo and C2'-endo, conformations are found in the deoxyribonucleotides. The minor groove, width (8.5 to 10.5 A) is intermediate between standard values for A (11 A), and B-form (7.4 A) DNA. The global parameters rise and base-pairs tilt (or, inclination) are like that of A-DNA, however the slide and x displacement, (Dx) are more like that of A-RNA, thus giving the hybrid a unique, conformation. In addition, the 10-mer crystallizes in a manner that allows, the formation of dimers that stack end-to-end, thereby providing a glimpse, of how an extended (20 base-pair) helix of RNA-DNA hybrid might appear., This duplex sequence was selected for study because it is specifically, recognized by the ribonuclease H function of HIV reverse transcriptase. A, structure of a substrate of this enzyme is of potential value in, understanding requirements for the selectivity of this important drug, target. The minor groove of the hybrid duplex, lined with the 2-OH of the, ribose rings, is the single distinguishing characteristic of the RNA/DNA, hybrid, undoubtedly an important structural feature conferring, selectivity.

About this Structure

1FIX is a Protein complex structure of sequences from [1]. Full crystallographic information is available from OCA.

Reference

The structure of an RNA/DNA hybrid: a substrate of the ribonuclease activity of HIV-1 reverse transcriptase., Horton NC, Finzel BC, J Mol Biol. 1996 Dec 6;264(3):521-33. PMID:8969302

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