1nlc

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1nlc, resolution 1.85Å

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HIV-1 DIS(Mal) duplex Zn-soaked

Overview

Metal ions, and magnesium in particular, are known to be involved in RNA, folding by stabilizing secondary and tertiary structures, and, as, cofactors, in RNA enzymatic activity. We have conducted a systematic, crystallographic analysis of cation binding to the duplex form of the, HIV-1 RNA dimerization initiation site for the subtype-A and -B natural, sequences. Eleven ions (K+, Pb2+, Mn2+, Ba2+, Ca2+, Cd2+, Sr2+, Zn2+, Co2+, Au3+ and Pt4+) and two hexammines [Co (NH3)6]3+ and [Ru (NH3)6]3+, were found to bind to the DIS duplex structure. Although the two sequences, are very similar, strong differences were found in their cation binding, properties. Divalent cations bind almost exclusively, as Mg2+, at, 'Hoogsteen' sites of guanine residues, with a cation-dependent affinity, for each site. Notably, a given cation can have very different affinities, for a priori equivalent sites within the same molecule. Surprisingly, none, of the two hexammines used were able to efficiently replace hexahydrated, magnesium. Instead, [Co (NH3)4]3+ was seen bound by inner-sphere, coordination to the RNA. This raises some questions about the practical, use of [Co (NH3)6]3+ as a [Mg (H2O)6]2+ mimetic. Also very unexpected was, the binding of the small Au3+ cation exactly between the Watson-Crick, sites of a G-C base pair after an obligatory deprotonation of N1 of the, guanine base. This extensive study of metal ion binding using X-ray, crystallography significantly enriches our knowledge on the binding of, middleweight or heavy metal ions to RNA, particularly compared with, magnesium.

About this Structure

1NLC is a Protein complex structure of sequences from [1] with ZN as ligand. Full crystallographic information is available from OCA.

Reference

A crystallographic study of the binding of 13 metal ions to two related RNA duplexes., Ennifar E, Walter P, Dumas P, Nucleic Acids Res. 2003 May 15;31(10):2671-82. PMID:12736317

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