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2fd0

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[[Image:2fd0.gif|left|200px]]<br /><applet load="2fd0" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:2fd0.gif|left|200px]]
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caption="2fd0, resolution 1.80&Aring;" />
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'''HIV-1 DIS kissing-loop in complex with lividomycin'''<br />
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{{Structure
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|PDB= 2fd0 |SIZE=350|CAPTION= <scene name='initialview01'>2fd0</scene>, resolution 1.80&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=LIV:(2R,3S,4S,5S,6R)-2-((2S,3S,4R,5R,6R)-5-AMINO-2-(AMINOMETHYL)-6-((2R,3S,4R,5S)-5-((1R,2R,3S,5R,6S)-3,5-DIAMINO-2-((2S,3R,5S,6R)-3-AMINO-5-HYDROXY-6-(HYDROXYMETHYL)-TETRAHYDRO-2H-PYRAN-2-YLOXY)-6-HYDROXYCYCLOHEXYLOXY)-4-HYDROXY-2-(HYDROXYMETHYL)-TETRAHYDROFURAN-3-YLOXY)-4-HYDROXY-TETRAHYDRO-2H-PYRAN-3-YLOXY)-6-(HYDROXYMETHYL)-TETRAHYDRO-2H-PYRAN-3,4,5-TRIOL'>LIV</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene> and <scene name='pdbligand=CL:CHLORIDE ION'>CL</scene>
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|ACTIVITY=
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|GENE=
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}}
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'''HIV-1 DIS kissing-loop in complex with lividomycin'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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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].
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2FD0 is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FD0 OCA].
==Reference==
==Reference==
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16679451 16679451]
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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:[http://www.ncbi.nlm.nih.gov/pubmed/16679451 16679451]
[[Category: Protein complex]]
[[Category: Protein complex]]
[[Category: Dumas, P.]]
[[Category: Dumas, P.]]
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[[Category: LIV]]
[[Category: LIV]]
[[Category: aminoglycoside]]
[[Category: aminoglycoside]]
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[[Category: antibiotics]]
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[[Category: antibiotic]]
[[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 Thu Feb 21 17:20:05 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 16:50:56 2008''

Revision as of 14:50, 20 March 2008


PDB ID 2fd0

Drag the structure with the mouse to rotate
, resolution 1.80Å
Ligands: , and
Coordinates: save as pdb, mmCIF, xml



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]. 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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