View source for 6onf


==Crystal structure of HIV-1 LM/HT Clade A/E CRF01 gp120 core in complex with (S)-MCG-III-188-A02.==
<StructureSection load='6onf' size='340' side='right'caption='[[6onf]], [[Resolution|resolution]] 1.84&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6onf]] is a 1 chain structure with sequence from [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=6ONF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ONF 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]] 1.842&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=MW4:ethyl+(3~{S})-3-[(4-chloranyl-3-fluoranyl-phenyl)carbamoyl]piperidine-1-carboxylate'>MW4</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=6onf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6onf OCA], [https://pdbe.org/6onf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6onf RCSB], [https://www.ebi.ac.uk/pdbsum/6onf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6onf ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A0M3KKW9_9HIV1 A0A0M3KKW9_9HIV1] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The HIV-1 envelope glycoprotein (Env) trimer mediates virus entry into cells. The "closed" conformation of Env is resistant to non-neutralizing antibodies (nnAbs). These antibodies mostly recognize occluded epitopes that can be exposed upon binding of CD4 or small-molecule CD4 mimetics (CD4mc). Here, we describe a new family of small molecules that expose Env to nnAbs and sensitize infected cells to antibody-dependent cellular cytotoxicity (ADCC). These compounds have limited capacity to inhibit virus infection directly, but are able to sensitize viral particles to neutralization by otherwise non-neutralizing antibodies. Structural analysis shows that some analogs of this family of CD4mc engage the gp120 Phe43 cavity by contacting the highly-conserved D368 residue, making them attractive scaffolds for drug development.IMPORTANCE HIV-1 has evolved multiple strategies to avoid humoral responses. One efficient mechanism is to keep its envelope glycoproteins (Env) in its "closed" conformation. Here we report on a new family of small molecules able to "open-up" Env, thus exposing vulnerable epitopes. This new family of molecules bind in the Phe43 cavity and contact the highly-conserved D368 residue. The structural and biological attributes of this family of molecules make them good candidates for drug development.

A new family of small-molecule CD4-mimetic compounds contact the highly conserved aspartic acid 368 of HIV-1 gp120 and mediates ADCC.,Ding S, Grenier MC, Tolbert WD, Vezina D, Sherburn R, Richard J, Prevost J, Chapleau JP, Gendron-Lepage G, Medjahed H, Abrams C, Sodroski J, Pazgier M, Smith AB 3rd, Finzi A J Virol. 2019 Sep 25. pii: JVI.01325-19. doi: 10.1128/JVI.01325-19. PMID:31554684<ref>PMID:31554684</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6onf" style="background-color:#fffaf0;"></div>

==See Also==
*[[Gp120 3D structures|Gp120 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human immunodeficiency virus 1]]
[[Category: Large Structures]]
[[Category: Pazgier M]]
[[Category: Sherburn R]]
[[Category: Tolbert WD]]