2fcz

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{{STRUCTURE_2fcz| PDB=2fcz | SCENE= }}
{{STRUCTURE_2fcz| PDB=2fcz | SCENE= }}
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'''HIV-1 DIS kissing-loop in complex with ribostamycin'''
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===HIV-1 DIS kissing-loop in complex with ribostamycin===
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==Overview==
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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.
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{{ABSTRACT_PUBMED_16679451}}
==About this Structure==
==About this Structure==
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[[Category: Hiv-1]]
[[Category: Hiv-1]]
[[Category: Rna]]
[[Category: Rna]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 03:44:53 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 03:00:27 2008''

Revision as of 00:00, 28 July 2008

Image:2fcz.png

Template:STRUCTURE 2fcz

HIV-1 DIS kissing-loop in complex with ribostamycin

Template:ABSTRACT PUBMED 16679451

About this Structure

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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