2fcz: Difference between revisions

Latest revision as of 09:25, 30 August 2023

HIV-1 DIS kissing-loop in complex with ribostamycin

Structural highlights

2fcz is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.01Å
Ligands:	5BU, K, RIO
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

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.

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Ennifar E, Paillart JC, Bodlenner A, Walter P, Weibel JM, Aubertin AM, Pale P, Dumas P, Marquet R. Targeting the dimerization initiation site of HIV-1 RNA with aminoglycosides: from crystal to cell. Nucleic Acids Res. 2006 May 5;34(8):2328-39. Print 2006. PMID:16679451 doi:34/8/2328

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Ennifar E, Paillart JC, Bodlenner A, Walter P, Weibel JM, Aubertin AM, Pale P, Dumas P, Marquet R. Targeting the dimerization initiation site of HIV-1 RNA with aminoglycosides: from crystal to cell. Nucleic Acids Res. 2006 May 5;34(8):2328-39. Print 2006. PMID:16679451 doi:34/8/2328

[1]

@@ Line 1: / Line 1: @@
-{{Seed}}
-[[Image:2fcz.png|left|200px]]
-<!--
+==HIV-1 DIS kissing-loop in complex with ribostamycin==
-The line below this paragraph, containing "STRUCTURE_2fcz", creates the "Structure Box" on the page.
+<StructureSection load='2fcz' size='340' side='right'caption='[[2fcz]], [[Resolution|resolution]] 2.01&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'>[[2fcz]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FCZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2FCZ 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]] 2.01&#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=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=RIO:RIBOSTAMYCIN'>RIO</scene></td></tr>
-{{STRUCTURE_2fcz|  PDB=2fcz  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2fcz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fcz OCA], [https://pdbe.org/2fcz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2fcz RCSB], [https://www.ebi.ac.uk/pdbsum/2fcz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2fcz ProSAT]</span></td></tr>
+</table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+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.
-===HIV-1 DIS kissing-loop in complex with ribostamycin===
+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<ref>PMID:16679451</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-<!--
+</div>
-The line below this paragraph, {{ABSTRACT_PUBMED_16679451}}, adds the Publication Abstract to the page
+<div class="pdbe-citations 2fcz" style="background-color:#fffaf0;"></div>
-(as it appears on PubMed at http://www.pubmed.gov), where 16679451 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_16679451}}
+__TOC__
+</StructureSection>
-==About this Structure==
+[[Category: Large Structures]]
-Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FCZ OCA].
+[[Category: Dumas P]]
+[[Category: Ennifar E]]
-==Reference==
+[[Category: Marquet R]]
-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: Paillart JC]]
-[[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 Mon Jul 28 03:00:27 2008''

2fcz: Difference between revisions

Latest revision as of 09:25, 30 August 2023

HIV-1 DIS kissing-loop in complex with ribostamycin

Structural highlights

Publication Abstract from PubMed

References

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