View source for 9bxy


==CRYSTAL STRUCTURE OF HIV-1 LM/HS CLADE A/E CRF01 GP120 CORE IN COMPLEX WITH DL-III-117==
<StructureSection load='9bxy' size='340' side='right'caption='[[9bxy]], [[Resolution|resolution]] 2.11&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9bxy]] 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=9BXY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9BXY 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]] 2.11&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1ATE:(3S,5R)-1-[4-(1-carbamimidoyl-L-prolyl)piperazine-1-carbonyl]-N-(4-chloro-3-fluorophenyl)-5-(hydroxymethyl)piperidine-3-carboxamide'>A1ATE</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</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=9bxy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9bxy OCA], [https://pdbe.org/9bxy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9bxy RCSB], [https://www.ebi.ac.uk/pdbsum/9bxy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9bxy ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A0M3KKW9_HV1 A0A0M3KKW9_HV1] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The ability of the HIV-1 accessory proteins Nef and Vpu to decrease CD4 protects infected cells from antibody-dependent cellular cytotoxicity (ADCC) by limiting the exposure of vulnerable epitopes to envelope glycoprotein (Env). Small-molecule CD4 mimetics (CD4mcs) based on piperidine scaffolds represent a new family of agents capable of sensitizing HIV-1-infected cells to ADCC by exposing CD4-induced (CD4i) epitopes on Env that are recognized by non-neutralizing antibodies which are abundant in plasma of people living with HIV. Here, we employed the combined methods of parallel synthesis, structure-based design, and optimization to generate a new line of piperidine-based CD4mcs, which sensitize HIV-1 infected cells to ADCC activity. The X-ray crystallographic study of the CD4mcs within the gp120 residues suggests that the positioning of the CD4mc inside the Phe43 cavity and synergistic contact of the CD4mc with the beta(20-21) loop and the alpha(1)-helix lead to improved antiviral activity.

Optimization of a Piperidine CD4-Mimetic Scaffold Sensitizing HIV-1 Infected Cells to Antibody-Dependent Cellular Cytotoxicity.,Lee D, Niu L, Ding S, Zhu H, Tolbert WD, Medjahed H, Beaudoin-Bussieres G, Abrams C, Finzi A, Pazgier M, Smith AB 3rd ACS Med Chem Lett. 2024 Oct 28;15(11):1961-1969. doi: , 10.1021/acsmedchemlett.4c00403. eCollection 2024 Nov 14. PMID:39563795<ref>PMID:39563795</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9bxy" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human immunodeficiency virus 1]]
[[Category: Large Structures]]
[[Category: Niu L]]
[[Category: Pazgier M]]
[[Category: Tolbert WD]]