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124d

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124d

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STRUCTURE OF A DNA:RNA HYBRID DUPLEX: WHY RNASE H DOES NOT CLEAVE PURE RNA

Overview

The solution structure of the DNA:RNA hybrid duplex d(GTCACATG):r(caugugac) has been determined by means of two-dimensional nuclear Overhauser effect (2D-NOE) spectra, restrained molecular dynamics and full-relaxation matrix stimulation of the 2D-NOE spectra. The DNA:RNA hybrid duplex assumes neither an A-form nor a B-form structure in solution, but an intermediate heteromerous duplex structure. The sugars of the RNA strand have a normal N-type C3'-endo conformation, but the DNA strand sugars have neither N-type nor S-type conformations; instead, they have an unexpected intermediate O4'-endo conformation. The negative x-displacement, as well as the small rise and positive inclination of the base-pairs, resembles A-form morphology but the minor groove width is intermediate between that of A-form and B-form duplexes. Both the DNA and RNA strands show prominent sequence-dependent variations in their helical parameters. Combined analysis of NOE and J-coupling data indicates that the DNA sugars are not in a dynamical two-state equilibrium. The detailed three-dimensional structure of this DNA:RNA hybrid molecule leads to a proposed model for its interaction with RNase H. Several specific structural features of the enzyme complexed with the hybrid duplex appear to explain the mechanism whereby RNase H discriminates between DNA:RNA hybrid duplexes and pure RNA:RNA duplexes.

About this Structure

124D is a Protein complex structure of sequences from [1]. Full crystallographic information is available from OCA.

Reference

Structure of a DNA:RNA hybrid duplex. Why RNase H does not cleave pure RNA., Fedoroff OYu, Salazar M, Reid BR, J Mol Biol. 1993 Oct 5;233(3):509-23. PMID:8411159

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