2fcz

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[[Image:2fcz.gif|left|200px]]
[[Image:2fcz.gif|left|200px]]
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{{Structure
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<!--
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|PDB= 2fcz |SIZE=350|CAPTION= <scene name='initialview01'>2fcz</scene>, resolution 2.01&Aring;
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The line below this paragraph, containing "STRUCTURE_2fcz", creates the "Structure Box" on the page.
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|SITE=
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|LIGAND= <scene name='pdbligand=5BU:5-BROMO-URIDINE-5&#39;-MONOPHOSPHATE'>5BU</scene>, <scene name='pdbligand=A:ADENOSINE-5&#39;-MONOPHOSPHATE'>A</scene>, <scene name='pdbligand=C:CYTIDINE-5&#39;-MONOPHOSPHATE'>C</scene>, <scene name='pdbligand=G:GUANOSINE-5&#39;-MONOPHOSPHATE'>G</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=RIO:RIBOSTAMYCIN'>RIO</scene>, <scene name='pdbligand=U:URIDINE-5&#39;-MONOPHOSPHATE'>U</scene>
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|GENE=
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{{STRUCTURE_2fcz| PDB=2fcz | SCENE= }}
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|RELATEDENTRY=[[2fcx|2FCX]], [[2fcy|2FCY]], [[1xp7|1XP7]], [[1y3s|1Y3S]], [[2fd0|2FD0]]
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2fcz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fcz OCA], [http://www.ebi.ac.uk/pdbsum/2fcz PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2fcz RCSB]</span>
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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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==About this Structure==
==About this Structure==
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2FCZ 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=2FCZ OCA].
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Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FCZ OCA].
==Reference==
==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:[http://www.ncbi.nlm.nih.gov/pubmed/16679451 16679451]
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]
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[[Category: Protein complex]]
 
[[Category: Dumas, P.]]
[[Category: Dumas, P.]]
[[Category: Ennifar, E.]]
[[Category: Ennifar, E.]]
[[Category: Marquet, R.]]
[[Category: Marquet, R.]]
[[Category: Paillart, J C.]]
[[Category: Paillart, J C.]]
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[[Category: aminoglycoside]]
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[[Category: Aminoglycoside]]
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[[Category: antibiotic]]
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[[Category: Antibiotic]]
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[[Category: hiv-1]]
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[[Category: Hiv-1]]
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[[Category: rna]]
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[[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 Mar 31 03:01:03 2008''
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Revision as of 00:44, 4 May 2008

Image:2fcz.gif

Template:STRUCTURE 2fcz

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

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 Sun May 4 03:44:53 2008

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