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2fcx

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(New page: 200px<br /> <applet load="2fcx" size="450" color="white" frame="true" align="right" spinBox="true" caption="2fcx, resolution 2.00&Aring;" /> '''HIV-1 DIS kissing-l...)
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[[Image:2fcx.gif|left|200px]]<br />
 
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<applet load="2fcx" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="2fcx, resolution 2.00&Aring;" />
 
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'''HIV-1 DIS kissing-loop in complex with neamine'''<br />
 
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==Overview==
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==HIV-1 DIS kissing-loop in complex with neamine==
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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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<StructureSection load='2fcx' size='340' side='right'caption='[[2fcx]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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== Structural highlights ==
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==About this Structure==
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<table><tr><td colspan='2'>[[2fcx]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FCX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2FCX FirstGlance]. <br>
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2FCX is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with K, CL and XXX as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2FCX OCA].
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5BU:5-BROMO-URIDINE-5-MONOPHOSPHATE'>5BU</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=XXX:(2R,3S,4R,5R,6R)-6-((1R,2R,3S,4R,6S)-4,6-DIAMINO-2,3-DIHYDROXYCYCLOHEXYLOXY)-5-AMINO-2-(AMINOMETHYL)-TETRAHYDRO-2H-PYRAN-3,4-DIOL'>XXX</scene></td></tr>
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==Reference==
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2fcx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fcx OCA], [https://pdbe.org/2fcx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2fcx RCSB], [https://www.ebi.ac.uk/pdbsum/2fcx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2fcx ProSAT]</span></td></tr>
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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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</table>
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[[Category: Protein complex]]
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__TOC__
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[[Category: Dumas, P.]]
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</StructureSection>
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[[Category: Ennifar, E.]]
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[[Category: Large Structures]]
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[[Category: Marquet, R.]]
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[[Category: Dumas P]]
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[[Category: Paillart, J.C.]]
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[[Category: Ennifar E]]
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[[Category: CL]]
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[[Category: Marquet R]]
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[[Category: K]]
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[[Category: Paillart JC]]
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[[Category: XXX]]
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[[Category: aminoglycoside]]
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[[Category: antibiotics]]
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[[Category: hiv-1]]
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[[Category: rna]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Thu Nov 8 14:46:55 2007''
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Current revision

HIV-1 DIS kissing-loop in complex with neamine

PDB ID 2fcx

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