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[[Image:2fcx.gif|left|200px]]


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==HIV-1 DIS kissing-loop in complex with neamine==
The line below this paragraph, containing "STRUCTURE_2fcx", creates the "Structure Box" on the page.
<StructureSection load='2fcx' size='340' side='right'caption='[[2fcx]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
You may change the PDB parameter (which sets the PDB file loaded into the applet)
== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<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>
or leave the SCENE parameter empty for the default display.
</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>
-->
<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>
{{STRUCTURE_2fcx|  PDB=2fcx  |  SCENE= }}
<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>
 
</table>
'''HIV-1 DIS kissing-loop in complex with neamine'''
__TOC__
 
</StructureSection>
 
[[Category: Large Structures]]
==Overview==
[[Category: Dumas P]]
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.
[[Category: Ennifar E]]
 
[[Category: Marquet R]]
==About this Structure==
[[Category: Paillart JC]]
Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FCX 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:[http://www.ncbi.nlm.nih.gov/pubmed/16679451 16679451]
[[Category: Dumas, P.]]
[[Category: Ennifar, E.]]
[[Category: Marquet, R.]]
[[Category: Paillart, J C.]]
[[Category: Aminoglycoside]]
[[Category: Antibiotic]]
[[Category: Hiv-1]]
[[Category: Rna]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 03:44:46 2008''

Latest revision as of 09:22, 14 February 2024

HIV-1 DIS kissing-loop in complex with neamine

2fcx, resolution 2.00Å

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