6opp: Difference between revisions
No edit summary |
No edit summary |
||
| (One intermediate revision by the same user not shown) | |||
| Line 1: | Line 1: | ||
==Asymmetric model of CD4- and 17-bound B41 HIV-1 Env SOSIP in complex with DDM== | |||
<StructureSection load='6opp' size='340' side='right'caption='[[6opp]], [[Resolution|resolution]] 3.70Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6opp]] is a 15 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OPP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OPP FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.7Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=LMT:DODECYL-BETA-D-MALTOSIDE'>LMT</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=6opp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6opp OCA], [https://pdbe.org/6opp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6opp RCSB], [https://www.ebi.ac.uk/pdbsum/6opp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6opp ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/B3UEZ6_9HIV1 B3UEZ6_9HIV1] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Disruption of viral fusion represents a viable, albeit under-explored, target for HIV therapeutics. Here, while studying the receptor-bound envelope glycoprotein conformation by cryoelectron microscopy (cryo-EM), we identify a pocket near the base of the trimer containing a bound detergent molecule and perform in silico drug screening by using a library of drug-like and commercially available molecules. After down-selection, we solve cryo-EM structures that validate the binding of two small molecule hits in very similar manners to the predicted binding poses, including interactions with aromatic residues within the fusion peptide. One of the molecules demonstrates low micromolar inhibition of the autologous virus by using a very rare phenylalanine in the fusion peptide and stabilizing the surrounding region. This work demonstrates that small molecules can target the fusion process, providing an additional target for anti-HIV therapeutics, and highlights the need to explore how fusion peptide sequence variations affect receptor-mediated conformational states across diverse HIV strains. | |||
A Strain-Specific Inhibitor of Receptor-Bound HIV-1 Targets a Pocket near the Fusion Peptide.,Ozorowski G, Torres JL, Santos-Martins D, Forli S, Ward AB Cell Rep. 2020 Nov 24;33(8):108428. doi: 10.1016/j.celrep.2020.108428. PMID:33238117<ref>PMID:33238117</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 6opp" style="background-color:#fffaf0;"></div> | ||
[[Category: Ozorowski | |||
[[Category: Torres | ==See Also== | ||
*[[Gp41 3D Structures|Gp41 3D Structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Human immunodeficiency virus 1]] | |||
[[Category: Large Structures]] | |||
[[Category: Ozorowski G]] | |||
[[Category: Torres JL]] | |||
[[Category: Ward AB]] | |||
Latest revision as of 13:18, 23 October 2024
Asymmetric model of CD4- and 17-bound B41 HIV-1 Env SOSIP in complex with DDMAsymmetric model of CD4- and 17-bound B41 HIV-1 Env SOSIP in complex with DDM
Structural highlights
FunctionPublication Abstract from PubMedDisruption of viral fusion represents a viable, albeit under-explored, target for HIV therapeutics. Here, while studying the receptor-bound envelope glycoprotein conformation by cryoelectron microscopy (cryo-EM), we identify a pocket near the base of the trimer containing a bound detergent molecule and perform in silico drug screening by using a library of drug-like and commercially available molecules. After down-selection, we solve cryo-EM structures that validate the binding of two small molecule hits in very similar manners to the predicted binding poses, including interactions with aromatic residues within the fusion peptide. One of the molecules demonstrates low micromolar inhibition of the autologous virus by using a very rare phenylalanine in the fusion peptide and stabilizing the surrounding region. This work demonstrates that small molecules can target the fusion process, providing an additional target for anti-HIV therapeutics, and highlights the need to explore how fusion peptide sequence variations affect receptor-mediated conformational states across diverse HIV strains. A Strain-Specific Inhibitor of Receptor-Bound HIV-1 Targets a Pocket near the Fusion Peptide.,Ozorowski G, Torres JL, Santos-Martins D, Forli S, Ward AB Cell Rep. 2020 Nov 24;33(8):108428. doi: 10.1016/j.celrep.2020.108428. PMID:33238117[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||