2r3c
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| - | [[Image:2r3c.gif|left|200px]]<br /><applet load="2r3c" size="350" color="white" frame="true" align="right" spinBox="true" | ||
| - | caption="2r3c, resolution 1.730Å" /> | ||
| - | '''Structure of the gp41 N-peptide in complex with the HIV entry inhibitor PIE1'''<br /> | ||
| - | == | + | ==Structure of the gp41 N-peptide in complex with the HIV entry inhibitor PIE1== |
| + | <StructureSection load='2r3c' size='340' side='right'caption='[[2r3c]], [[Resolution|resolution]] 1.73Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[2r3c]] is a 4 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=2R3C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2R3C 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]] 1.73Å</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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DAL:D-ALANINE'>DAL</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=DSN:D-SERINE'>DSN</scene>, <scene name='pdbligand=DTR:D-TRYPTOPHAN'>DTR</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=YT3:YTTRIUM+(III)+ION'>YT3</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=2r3c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2r3c OCA], [https://pdbe.org/2r3c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2r3c RCSB], [https://www.ebi.ac.uk/pdbsum/2r3c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2r3c 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. | 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> | |
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| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 2r3c" style="background-color:#fffaf0;"></div> | |
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| - | + | ==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]] | ||
Current revision
Structure of the gp41 N-peptide in complex with the HIV entry inhibitor PIE1
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