2l8h
From Proteopedia
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==Chemical probe bound to HIV TAR RNA== | ==Chemical probe bound to HIV TAR RNA== | ||
| - | <StructureSection load='2l8h' size='340' side='right' caption='[[2l8h | + | <StructureSection load='2l8h' size='340' side='right'caption='[[2l8h]]' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | [[2l8h]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2L8H OCA]. <br> | + | <table><tr><td colspan='2'>[[2l8h]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2L8H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2L8H FirstGlance]. <br> |
| - | <b> | + | </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=ARG:ARGININE'>ARG</scene>, <scene name='pdbligand=L8H:4-METHOXYNAPHTHALEN-2-AMINE'>L8H</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2l8h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l8h OCA], [https://pdbe.org/2l8h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2l8h RCSB], [https://www.ebi.ac.uk/pdbsum/2l8h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2l8h ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
The HIV-1 transactivation response (TAR) element-Tat interaction is a potentially valuable target for treating HIV infection, but efforts to develop TAR-binding antiviral drugs have not yet yielded a successful candidate for clinical development. In this work, we describe a novel approach toward screening fragments against RNA that uses a chemical probe to target the Tat-binding region of TAR. This probe fulfills two critical roles in the screen: by locking the RNA into a conformation capable of binding other fragments, it simultaneously allows the identification of proximal binding fragments by ligand-based NMR. Using this approach, we have discovered six novel TAR-binding fragments, three of which were docked relative to the probe-RNA structure using experimental NMR restraints. The consistent orientations of functional groups in our data-driven docked structures and common electrostatic properties across all fragment leads reveal a surprising level of selectivity by our fragment-sized screening hits. These models further suggest linking strategies for the development of higher-affinity lead compounds for the inhibition of the TAR-Tat interaction. | The HIV-1 transactivation response (TAR) element-Tat interaction is a potentially valuable target for treating HIV infection, but efforts to develop TAR-binding antiviral drugs have not yet yielded a successful candidate for clinical development. In this work, we describe a novel approach toward screening fragments against RNA that uses a chemical probe to target the Tat-binding region of TAR. This probe fulfills two critical roles in the screen: by locking the RNA into a conformation capable of binding other fragments, it simultaneously allows the identification of proximal binding fragments by ligand-based NMR. Using this approach, we have discovered six novel TAR-binding fragments, three of which were docked relative to the probe-RNA structure using experimental NMR restraints. The consistent orientations of functional groups in our data-driven docked structures and common electrostatic properties across all fragment leads reveal a surprising level of selectivity by our fragment-sized screening hits. These models further suggest linking strategies for the development of higher-affinity lead compounds for the inhibition of the TAR-Tat interaction. | ||
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A Small-Molecule Probe Induces a Conformation in HIV TAR RNA Capable of Binding Drug-Like Fragments.,Davidson A, Begley DW, Lau C, Varani G J Mol Biol. 2011 Jul 29;410(5):984-96. PMID:21763501<ref>PMID:21763501</ref> | A Small-Molecule Probe Induces a Conformation in HIV TAR RNA Capable of Binding Drug-Like Fragments.,Davidson A, Begley DW, Lau C, Varani G J Mol Biol. 2011 Jul 29;410(5):984-96. PMID:21763501<ref>PMID:21763501</ref> | ||
| - | From | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| + | </div> | ||
| + | <div class="pdbe-citations 2l8h" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: Begley | + | [[Category: Large Structures]] |
| - | [[Category: Davidson | + | [[Category: Synthetic construct]] |
| - | [[Category: Lau | + | [[Category: Begley D]] |
| - | [[Category: Varani | + | [[Category: Davidson A]] |
| - | + | [[Category: Lau C]] | |
| + | [[Category: Varani G]] | ||
Current revision
Chemical probe bound to HIV TAR RNA
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