2kx5: Difference between revisions
m Protected "2kx5" [edit=sysop:move=sysop] |
No edit summary |
||
| (9 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
< | ==Recognition of HIV TAR RNA by peptide mimetic of Tat protein== | ||
<StructureSection load='2kx5' size='340' side='right'caption='[[2kx5]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2kx5]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KX5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KX5 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 10 models</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DPR:D-PROLINE'>DPR</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=2kx5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kx5 OCA], [https://pdbe.org/2kx5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kx5 RCSB], [https://www.ebi.ac.uk/pdbsum/2kx5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kx5 ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The pharmacological disruption of the interaction between the HIV Tat protein and its cognate transactivation response RNA (TAR) would generate novel anti-viral drugs with a low susceptibility to drug resistance, but efforts to discover ligands with sufficient potency to warrant pharmaceutical development have been unsuccessful. We have previously described a family of structurally constrained beta-hairpin peptides that potently inhibits viral growth in HIV-infected cells. The nuclear magnetic resonance (NMR) structure of an inhibitory complex revealed that the peptide makes intimate contacts with the 3-nt bulge and the upper helix of the RNA hairpin, but that a single residue contacts the apical loop where recruitment of the essential cellular co-factor cyclin T(1) occurs. Attempting to extend the peptide to form more interactions with the RNA loop, we examined a library of longer peptides and achieved >6-fold improvement in affinity. The structure of TAR bound to one of the extended peptides reveals that the peptide slides down the major groove of the RNA, relative to our design, in order to maintain critical interactions with TAR. These conserved contacts involve three amino acid side chains and identify critical interaction points required for potent and specific binding to TAR RNA. They constitute a template of essential interactions required for inhibition of this RNA. | |||
Essential structural requirements for specific recognition of HIV TAR RNA by peptide mimetics of Tat protein.,Davidson A, Patora-Komisarska K, Robinson JA, Varani G Nucleic Acids Res. 2010 Aug 19. PMID:20724442<ref>PMID:20724442</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2kx5" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Tat protein|Tat protein]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | [[Category: Large Structures]] | ||
[[ | [[Category: Davidson A]] | ||
[[Category: Patora-Komisarska K]] | |||
== | [[Category: Robinson J]] | ||
< | [[Category: Varani G]] | ||
[[Category: Davidson | |||
[[Category: Patora-Komisarska | |||
[[Category: Robinson | |||
[[Category: Varani | |||
Latest revision as of 04:08, 21 November 2024
Recognition of HIV TAR RNA by peptide mimetic of Tat proteinRecognition of HIV TAR RNA by peptide mimetic of Tat protein
Structural highlights
Publication Abstract from PubMedThe pharmacological disruption of the interaction between the HIV Tat protein and its cognate transactivation response RNA (TAR) would generate novel anti-viral drugs with a low susceptibility to drug resistance, but efforts to discover ligands with sufficient potency to warrant pharmaceutical development have been unsuccessful. We have previously described a family of structurally constrained beta-hairpin peptides that potently inhibits viral growth in HIV-infected cells. The nuclear magnetic resonance (NMR) structure of an inhibitory complex revealed that the peptide makes intimate contacts with the 3-nt bulge and the upper helix of the RNA hairpin, but that a single residue contacts the apical loop where recruitment of the essential cellular co-factor cyclin T(1) occurs. Attempting to extend the peptide to form more interactions with the RNA loop, we examined a library of longer peptides and achieved >6-fold improvement in affinity. The structure of TAR bound to one of the extended peptides reveals that the peptide slides down the major groove of the RNA, relative to our design, in order to maintain critical interactions with TAR. These conserved contacts involve three amino acid side chains and identify critical interaction points required for potent and specific binding to TAR RNA. They constitute a template of essential interactions required for inhibition of this RNA. Essential structural requirements for specific recognition of HIV TAR RNA by peptide mimetics of Tat protein.,Davidson A, Patora-Komisarska K, Robinson JA, Varani G Nucleic Acids Res. 2010 Aug 19. PMID:20724442[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||