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| [[Image:2fcx.gif|left|200px]]<br /><applet load="2fcx" size="350" color="white" frame="true" align="right" spinBox="true"
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| caption="2fcx, resolution 2.00Å" />
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| '''HIV-1 DIS kissing-loop in complex with neamine'''<br />
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| ==Overview== | | ==HIV-1 DIS kissing-loop in complex with neamine== |
| 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.
| | <StructureSection load='2fcx' size='340' side='right'caption='[[2fcx]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | | == Structural highlights == |
| ==About this Structure== | | <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> |
| 2FCX is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=K:'>K</scene>, <scene name='pdbligand=CL:'>CL</scene> and <scene name='pdbligand=XXX:'>XXX</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FCX OCA].
| | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> |
| | | <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> |
| ==Reference==
| | <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> |
| 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]
| | </table> |
| [[Category: Protein complex]] | | __TOC__ |
| [[Category: Dumas, P.]] | | </StructureSection> |
| [[Category: Ennifar, E.]] | | [[Category: Large Structures]] |
| [[Category: Marquet, R.]] | | [[Category: Dumas P]] |
| [[Category: Paillart, J C.]] | | [[Category: Ennifar E]] |
| [[Category: CL]]
| | [[Category: Marquet R]] |
| [[Category: K]]
| | [[Category: Paillart JC]] |
| [[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://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:20:05 2008''
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