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==CRYSTAL STRUCTURE OF THE D10-P1/IQN17 COMPLEX: A D-PEPTIDE INHIBITOR OF HIV-1 ENTRY BOUND TO THE GP41 COILED-COIL POCKET.== | |||
<StructureSection load='1czq' size='340' side='right'caption='[[1czq]], [[Resolution|resolution]] 1.50Å' scene=''> | |||
== Structural highlights == | |||
| | <table><tr><td colspan='2'>[[1czq]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus Human immunodeficiency virus] and [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CZQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1CZQ FirstGlance]. <br> | ||
</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=DAR:D-ARGININE'>DAR</scene>, <scene name='pdbligand=DCY:D-CYSTEINE'>DCY</scene>, <scene name='pdbligand=DGL:D-GLUTAMIC+ACID'>DGL</scene>, <scene name='pdbligand=DHI:D-HISTIDINE'>DHI</scene>, <scene name='pdbligand=DLE:D-LEUCINE'>DLE</scene>, <scene name='pdbligand=DTR:D-TRYPTOPHAN'>DTR</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=1czq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1czq OCA], [https://pdbe.org/1czq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1czq RCSB], [https://www.ebi.ac.uk/pdbsum/1czq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1czq ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
== | |||
The HIV-1 gp41 protein promotes viral entry by mediating the fusion of viral and cellular membranes. A prominent pocket on the surface of a central trimeric coiled coil within gp41 was previously identified as a potential target for drugs that inhibit HIV-1 entry. We designed a peptide, IQN17, which properly presents this pocket. Utilizing IQN17 and mirror-image phage display, we identified cyclic, D-peptide inhibitors of HIV-1 infection that share a sequence motif. A 1.5 A cocrystal structure of IQN17 in complex with a D-peptide, and NMR studies, show that conserved residues of these inhibitors make intimate contact with the gp41 pocket. Our studies validate the pocket per se as a target for drug development. IQN17 and these D-peptide inhibitors are likely to be useful for development and identification of a new class of orally bioavailable anti-HIV drugs. | The HIV-1 gp41 protein promotes viral entry by mediating the fusion of viral and cellular membranes. A prominent pocket on the surface of a central trimeric coiled coil within gp41 was previously identified as a potential target for drugs that inhibit HIV-1 entry. We designed a peptide, IQN17, which properly presents this pocket. Utilizing IQN17 and mirror-image phage display, we identified cyclic, D-peptide inhibitors of HIV-1 infection that share a sequence motif. A 1.5 A cocrystal structure of IQN17 in complex with a D-peptide, and NMR studies, show that conserved residues of these inhibitors make intimate contact with the gp41 pocket. Our studies validate the pocket per se as a target for drug development. IQN17 and these D-peptide inhibitors are likely to be useful for development and identification of a new class of orally bioavailable anti-HIV drugs. | ||
Inhibiting HIV-1 entry: discovery of D-peptide inhibitors that target the gp41 coiled-coil pocket.,Eckert DM, Malashkevich VN, Hong LH, Carr PA, Kim PS Cell. 1999 Oct 1;99(1):103-15. PMID:10520998<ref>PMID:10520998</ref> | |||
Inhibiting HIV-1 entry: discovery of D-peptide inhibitors that target the gp41 coiled-coil pocket., Eckert DM, Malashkevich VN, Hong LH, Carr PA, Kim PS | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1czq" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Human immunodeficiency virus]] | |||
[[Category: Large Structures]] | |||
[[Category: Saccharomyces cerevisiae]] | |||
[[Category: Carr PA]] | |||
[[Category: Eckert DM]] | |||
[[Category: Hong LH]] | |||
[[Category: Kim PS]] | |||
[[Category: Malashkevich VN]] | |||
Latest revision as of 11:48, 7 December 2022
CRYSTAL STRUCTURE OF THE D10-P1/IQN17 COMPLEX: A D-PEPTIDE INHIBITOR OF HIV-1 ENTRY BOUND TO THE GP41 COILED-COIL POCKET.CRYSTAL STRUCTURE OF THE D10-P1/IQN17 COMPLEX: A D-PEPTIDE INHIBITOR OF HIV-1 ENTRY BOUND TO THE GP41 COILED-COIL POCKET.
Structural highlights
Publication Abstract from PubMedThe HIV-1 gp41 protein promotes viral entry by mediating the fusion of viral and cellular membranes. A prominent pocket on the surface of a central trimeric coiled coil within gp41 was previously identified as a potential target for drugs that inhibit HIV-1 entry. We designed a peptide, IQN17, which properly presents this pocket. Utilizing IQN17 and mirror-image phage display, we identified cyclic, D-peptide inhibitors of HIV-1 infection that share a sequence motif. A 1.5 A cocrystal structure of IQN17 in complex with a D-peptide, and NMR studies, show that conserved residues of these inhibitors make intimate contact with the gp41 pocket. Our studies validate the pocket per se as a target for drug development. IQN17 and these D-peptide inhibitors are likely to be useful for development and identification of a new class of orally bioavailable anti-HIV drugs. Inhibiting HIV-1 entry: discovery of D-peptide inhibitors that target the gp41 coiled-coil pocket.,Eckert DM, Malashkevich VN, Hong LH, Carr PA, Kim PS Cell. 1999 Oct 1;99(1):103-15. PMID:10520998[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References |
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