2fd0
From Proteopedia
(New page: 200px<br /> <applet load="2fd0" size="450" color="white" frame="true" align="right" spinBox="true" caption="2fd0, resolution 1.80Å" /> '''HIV-1 DIS kissing-l...) |
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| - | [[Image:2fd0.gif|left|200px]]<br /> | + | [[Image:2fd0.gif|left|200px]]<br /><applet load="2fd0" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2fd0" size=" | + | |
caption="2fd0, resolution 1.80Å" /> | caption="2fd0, resolution 1.80Å" /> | ||
'''HIV-1 DIS kissing-loop in complex with lividomycin'''<br /> | '''HIV-1 DIS kissing-loop in complex with lividomycin'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The kissing-loop complex that initiates dimerization of genomic RNA is | + | 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== | ==About this Structure== | ||
| - | 2FD0 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with LIV, K and CL as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 2FD0 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=LIV:'>LIV</scene>, <scene name='pdbligand=K:'>K</scene> and <scene name='pdbligand=CL:'>CL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FD0 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Ennifar, E.]] | [[Category: Ennifar, E.]] | ||
[[Category: Marquet, R.]] | [[Category: Marquet, R.]] | ||
| - | [[Category: Paillart, J | + | [[Category: Paillart, J C.]] |
[[Category: CL]] | [[Category: CL]] | ||
[[Category: K]] | [[Category: K]] | ||
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[[Category: rna]] | [[Category: rna]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:20:05 2008'' |
Revision as of 15:20, 21 February 2008
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HIV-1 DIS kissing-loop in complex with lividomycin
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
2FD0 is a Protein complex structure of sequences from [1] with , and 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
Page seeded by OCA on Thu Feb 21 17:20:05 2008
Categories: Protein complex | Dumas, P. | Ennifar, E. | Marquet, R. | Paillart, J C. | CL | K | LIV | Aminoglycoside | Antibiotics | Hiv-1 | Rna
