2fcx

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

|PDB= 2fcx |SIZE=350|CAPTION= <scene name='initialview01'>2fcx</scene>, resolution 2.00&Aring;

|SITE=

|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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=G:GUANOSINE-5&#39;-MONOPHOSPHATE'>G</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=U:URIDINE-5&#39;-MONOPHOSPHATE'>U</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>

|ACTIVITY=

|GENE=

|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2fcx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fcx OCA], [http://www.ebi.ac.uk/pdbsum/2fcx PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2fcx RCSB]</span>

 

 

 

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.

 

2FCX 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=2FCX OCA].

 

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: Dumas, P.]]

[[Category: Ennifar, E.]]

[[Category: Marquet, R.]]

[[Category: Paillart, J C.]]