2fcx: Difference between revisions
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[[Image:2fcx.gif|left|200px]] | [[Image:2fcx.gif|left|200px]] | ||
'''HIV-1 DIS kissing-loop in complex with neamine''' | {{Structure | ||
|PDB= 2fcx |SIZE=350|CAPTION= <scene name='initialview01'>2fcx</scene>, resolution 2.00Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene> and <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= | |||
}} | |||
'''HIV-1 DIS kissing-loop in complex with neamine''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
2FCX is a [ | 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]. | ||
==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:// | 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: Protein complex]] | ||
[[Category: Dumas, P.]] | [[Category: Dumas, P.]] | ||
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[[Category: XXX]] | [[Category: XXX]] | ||
[[Category: aminoglycoside]] | [[Category: aminoglycoside]] | ||
[[Category: | [[Category: antibiotic]] | ||
[[Category: hiv-1]] | [[Category: hiv-1]] | ||
[[Category: rna]] | [[Category: rna]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 16:50:55 2008'' | ||
Revision as of 14:50, 20 March 2008
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| 2fcx, resolution 2.00Å | |||||||||||||
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| Ligands: | K, CL and XXX | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
HIV-1 DIS kissing-loop in complex with neamine
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
2FCX is a Protein complex structure of sequences from [1]. 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
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