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==Structure of the gp41 N-trimer in complex with the HIV entry inhibitor PIE7== | |||
[[ | <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. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2R5D OCA]. <br> | |||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><br> | |||
<tr><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><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=NH2:AMINO+GROUP'>NH2</scene></td></tr> | |||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2r3c|2r3c]], [[2r5b|2r5b]]</td></tr> | |||
<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span></td></tr> | |||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2r5d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2r5d OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2r5d RCSB], [http://www.ebi.ac.uk/pdbsum/2r5d PDBsum]</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> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | |||
[[Category: Heroux, A.]] | [[Category: Heroux, A.]] | ||
[[Category: Hill, C P.]] | [[Category: Hill, C P.]] | ||
| Line 31: | Line 27: | ||
[[Category: Welch, B.]] | [[Category: Welch, B.]] | ||
[[Category: Hiv]] | [[Category: Hiv]] | ||
[[Category: Pie]] | [[Category: Pie]] | ||
[[Category: Viral entry]] | [[Category: Viral entry]] | ||
[[Category: Viral protein]] | [[Category: Viral protein-inhibitor complex]] | ||
Revision as of 11:41, 7 May 2014
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. References
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