2fcz

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Revision as of 12:41, 8 November 2007

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spinqualitylabelsall models 2fcz, resolution 2.01Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

HIV-1 DIS kissing-loop in complex with ribostamycin

Overview

The kissing-loop complex that initiates dimerization of genomic RNA is, crucial for Human Immunodeficiency Virus Type 1 (HIV-1) replication. We, showed that owing to its strong similitude with the bacterial ribosomal A, site it can be targeted by aminoglycosides. Here, we present its crystal, structure in complex with neamine, ribostamycin, neomycin and lividomycin., These structures explain the specificity for 4,5-disubstituted, 2-deoxystreptamine (DOS) derivatives and for subtype A and subtype F, kissing-loop complexes, and provide a strong basis for rational drug, design. As a consequence of the different topologies of the kissing-loop, complex and the A site, these aminoglycosides establish more contacts with, HIV-1 RNA than with 16S RNA. Together with biochemical experiments, they, showed that while rings I, II and III confer binding specificity, rings IV, and V are important for affinity. Binding of neomycin, paromomycin and, lividomycin strongly stabilized the kissing-loop complex by bridging the, two HIV-1 RNA molecules. Furthermore, in situ footprinting showed that the, dimerization initiation site (DIS) of HIV-1 genomic RNA could be targeted, by these aminoglycosides in infected cells and virions, demonstrating its, accessibility.

About this Structure

2FCZ is a Protein complex structure of sequences from [1] with K and RIO as ligands. Full crystallographic information is available from OCA.

Reference

Targeting the dimerization initiation site of HIV-1 RNA with aminoglycosides: from crystal to cell., Ennifar E, Paillart JC, Bodlenner A, Walter P, Weibel JM, Aubertin AM, Pale P, Dumas P, Marquet R, Nucleic Acids Res. 2006 May 5;34(8):2328-39. Print 2006. PMID:16679451

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