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New page: left|200px<br /><applet load="2r5d" size="350" color="white" frame="true" align="right" spinBox="true" caption="2r5d, resolution 1.660Å" /> '''Structure of the gp... |
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== | ==Structure of the gp41 N-trimer in complex with the HIV entry inhibitor PIE7== | ||
During HIV-1 entry, the highly conserved gp41 N-trimer pocket region | <StructureSection load='2r5d' size='340' side='right'caption='[[2r5d]], [[Resolution|resolution]] 1.66Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2r5d]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2R5D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2R5D FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.66Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=DAS:D-ASPARTIC+ACID'>DAS</scene>, <scene name='pdbligand=DCY:D-CYSTEINE'>DCY</scene>, <scene name='pdbligand=DGL:D-GLUTAMIC+ACID'>DGL</scene>, <scene name='pdbligand=DGN:D-GLUTAMINE'>DGN</scene>, <scene name='pdbligand=DLE:D-LEUCINE'>DLE</scene>, <scene name='pdbligand=DLY:D-LYSINE'>DLY</scene>, <scene name='pdbligand=DPR:D-PROLINE'>DPR</scene>, <scene name='pdbligand=DTR:D-TRYPTOPHAN'>DTR</scene>, <scene name='pdbligand=DTY:D-TYROSINE'>DTY</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=2r5d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2r5d OCA], [https://pdbe.org/2r5d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2r5d RCSB], [https://www.ebi.ac.uk/pdbsum/2r5d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2r5d ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
During HIV-1 entry, the highly conserved gp41 N-trimer pocket region becomes transiently exposed and vulnerable to inhibition. Using mirror-image phage display and structure-assisted design, we have discovered protease-resistant D-amino acid peptides (D-peptides) that bind the N-trimer pocket with high affinity and potently inhibit viral entry. We also report high-resolution crystal structures of two of these D-peptides in complex with a pocket mimic that suggest sources of their high potency. A trimeric version of one of these peptides is the most potent pocket-specific entry inhibitor yet reported by three orders of magnitude (IC(50) = 250 pM). These results are the first demonstration that D-peptides can form specific and high-affinity interactions with natural protein targets and strengthen their promise as therapeutic agents. The D-peptides described here address limitations associated with current L-peptide entry inhibitors and are promising leads for the prevention and treatment of HIV/AIDS. | |||
Potent D-peptide inhibitors of HIV-1 entry.,Welch BD, VanDemark AP, Heroux A, Hill CP, Kay MS Proc Natl Acad Sci U S A. 2007 Oct 23;104(43):16828-33. Epub 2007 Oct 17. PMID:17942675<ref>PMID:17942675</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2r5d" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Gp41 3D Structures|Gp41 3D Structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Synthetic construct]] | |||
[[Category: Heroux A]] | |||
[[Category: Hill CP]] | |||
[[Category: Kay MS]] | |||
[[Category: VanDemark AP]] | |||
[[Category: Welch B]] | |||
Latest revision as of 11:36, 30 October 2024
Structure of the gp41 N-trimer in complex with the HIV entry inhibitor PIE7Structure of the gp41 N-trimer in complex with the HIV entry inhibitor PIE7
Structural highlights
Publication Abstract from PubMedDuring HIV-1 entry, the highly conserved gp41 N-trimer pocket region becomes transiently exposed and vulnerable to inhibition. Using mirror-image phage display and structure-assisted design, we have discovered protease-resistant D-amino acid peptides (D-peptides) that bind the N-trimer pocket with high affinity and potently inhibit viral entry. We also report high-resolution crystal structures of two of these D-peptides in complex with a pocket mimic that suggest sources of their high potency. A trimeric version of one of these peptides is the most potent pocket-specific entry inhibitor yet reported by three orders of magnitude (IC(50) = 250 pM). These results are the first demonstration that D-peptides can form specific and high-affinity interactions with natural protein targets and strengthen their promise as therapeutic agents. The D-peptides described here address limitations associated with current L-peptide entry inhibitors and are promising leads for the prevention and treatment of HIV/AIDS. Potent D-peptide inhibitors of HIV-1 entry.,Welch BD, VanDemark AP, Heroux A, Hill CP, Kay MS Proc Natl Acad Sci U S A. 2007 Oct 23;104(43):16828-33. Epub 2007 Oct 17. PMID:17942675[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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