1uts: Difference between revisions

Latest revision as of 05:32, 15 May 2024

Designed HIV-1 TAR Binding Ligand

Structural highlights

1uts is a 1 chain structure with sequence from Human immunodeficiency virus 1. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR
Ligands:	P13
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

The targeting of RNA for the design of novel anti-viral compounds represents an area of vast potential. We have used NMR and computational methods to model the interaction of a series of synthetic inhibitors of the in vitro RNA binding activities of a peptide derived from the transcriptional activator protein, Tat, from human immunodeficiency virus type 1. Inhibition has been measured through the monitering of fluorescence resonance energy transfer between fluorescently labeled peptide and RNA components. A series of compounds containing a bi-aryl heterocycle as one of the three substituents on a benzylic scaffold, induce a novel, inactive TAR conformation by stacking between base-pairs at the site of a three-base bulge within TAR. The development of this series resulted in an enhancement in potency (with Ki < 100 nM in an in vitro assay) and the removal of problematic guanidinium moieties. Ligands from this series can act as inhibitors of Tat-induced transcription in a cell-free system. This study validates the drug design strategy of using a ligand to target the RNA receptor in a non-functional conformation.

Structure-based drug design targeting an inactive RNA conformation: exploiting the flexibility of HIV-1 TAR RNA.,Murchie AI, Davis B, Isel C, Afshar M, Drysdale MJ, Bower J, Potter AJ, Starkey ID, Swarbrick TM, Mirza S, Prescott CD, Vaglio P, Aboul-ela F, Karn J J Mol Biol. 2004 Feb 20;336(3):625-38. PMID:15095977^[1]

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

References

↑ Murchie AI, Davis B, Isel C, Afshar M, Drysdale MJ, Bower J, Potter AJ, Starkey ID, Swarbrick TM, Mirza S, Prescott CD, Vaglio P, Aboul-ela F, Karn J. Structure-based drug design targeting an inactive RNA conformation: exploiting the flexibility of HIV-1 TAR RNA. J Mol Biol. 2004 Feb 20;336(3):625-38. PMID:15095977 doi:10.1016/j.jmb.2003.12.028

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Murchie AI, Davis B, Isel C, Afshar M, Drysdale MJ, Bower J, Potter AJ, Starkey ID, Swarbrick TM, Mirza S, Prescott CD, Vaglio P, Aboul-ela F, Karn J. Structure-based drug design targeting an inactive RNA conformation: exploiting the flexibility of HIV-1 TAR RNA. J Mol Biol. 2004 Feb 20;336(3):625-38. PMID:15095977 doi:10.1016/j.jmb.2003.12.028

[1]

@@ Line 1: / Line 1: @@
-{{Seed}}
-[[Image:1uts.png|left|200px]]
-<!--
+==Designed HIV-1 TAR Binding Ligand==
-The line below this paragraph, containing "STRUCTURE_1uts", creates the "Structure Box" on the page.
+<StructureSection load='1uts' size='340' side='right'caption='[[1uts]]' 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'>[[1uts]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UTS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1UTS 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">Solution NMR</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=P13:N-[2-(3-AMINOPROPOXY)-5-(1H-INDOL-5-YL)BENZYL]-N-(2-PIPERAZIN-1-YLETHYL)AMINE'>P13</scene></td></tr>
-{{STRUCTURE_1uts|  PDB=1uts  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1uts FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1uts OCA], [https://pdbe.org/1uts PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1uts RCSB], [https://www.ebi.ac.uk/pdbsum/1uts PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1uts ProSAT]</span></td></tr>
+</table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The targeting of RNA for the design of novel anti-viral compounds represents an area of vast potential. We have used NMR and computational methods to model the interaction of a series of synthetic inhibitors of the in vitro RNA binding activities of a peptide derived from the transcriptional activator protein, Tat, from human immunodeficiency virus type 1. Inhibition has been measured through the monitering of fluorescence resonance energy transfer between fluorescently labeled peptide and RNA components. A series of compounds containing a bi-aryl heterocycle as one of the three substituents on a benzylic scaffold, induce a novel, inactive TAR conformation by stacking between base-pairs at the site of a three-base bulge within TAR. The development of this series resulted in an enhancement in potency (with Ki &lt; 100 nM in an in vitro assay) and the removal of problematic guanidinium moieties. Ligands from this series can act as inhibitors of Tat-induced transcription in a cell-free system. This study validates the drug design strategy of using a ligand to target the RNA receptor in a non-functional conformation.
-===DESIGNED HIV-1 TAR BINDING LIGAND===
+Structure-based drug design targeting an inactive RNA conformation: exploiting the flexibility of HIV-1 TAR RNA.,Murchie AI, Davis B, Isel C, Afshar M, Drysdale MJ, Bower J, Potter AJ, Starkey ID, Swarbrick TM, Mirza S, Prescott CD, Vaglio P, Aboul-ela F, Karn J J Mol Biol. 2004 Feb 20;336(3):625-38. PMID:15095977<ref>PMID:15095977</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_15095977}}, adds the Publication Abstract to the page
+<div class="pdbe-citations 1uts" style="background-color:#fffaf0;"></div>
-(as it appears on PubMed at http://www.pubmed.gov), where 15095977 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_15095977}}
+__TOC__
+</StructureSection>
-==About this Structure==
+[[Category: Human immunodeficiency virus 1]]
-UTS is a [[Single protein]] structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UTS OCA].
+[[Category: Large Structures]]
+[[Category: Aboul-Ela F]]
-==Reference==
+[[Category: Davis B]]
-Structure-based drug design targeting an inactive RNA conformation: exploiting the flexibility of HIV-1 TAR RNA., Murchie AI, Davis B, Isel C, Afshar M, Drysdale MJ, Bower J, Potter AJ, Starkey ID, Swarbrick TM, Mirza S, Prescott CD, Vaglio P, Aboul-ela F, Karn J, J Mol Biol. 2004 Feb 20;336(3):625-38. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15095977 15095977]
+[[Category: Karn J]]
-[[Category: Single protein]]
+[[Category: Murchie AIH]]
-[[Category: Aboul-Ela, F.]]
-[[Category: Davis, B.]]
-[[Category: Karn, J.]]
-[[Category: Murchie, A I.H.]]
-[[Category: Antiviral]]
-[[Category: Conformational change]]
-[[Category: Drug design]]
-[[Category: Hiv-1]]
-[[Category: Ligand binding]]
-[[Category: Tar rna]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 23:13:29 2008''

1uts: Difference between revisions

Latest revision as of 05:32, 15 May 2024

Designed HIV-1 TAR Binding Ligand

Structural highlights

Publication Abstract from PubMed

References

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