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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'''
| | ===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. | | The line below this paragraph, {{ABSTRACT_PUBMED_16679451}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 16679451 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_16679451}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Hiv-1]] | | [[Category: Hiv-1]] |
| [[Category: Rna]] | | [[Category: Rna]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 03:44:53 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 03:00:27 2008'' |
