View source for 8gd1


==Crystal Structure of HIV-1 LM/HT Clade A/E CRF01 GP120 Core in Complex with ZXC-I-092==
<StructureSection load='8gd1' size='340' side='right'caption='[[8gd1]], [[Resolution|resolution]] 2.85&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8gd1]] 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=8GD1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8GD1 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]] 2.85&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=Z1I:(3~{S},5~{S})-5-(aminomethyl)-~{N}-(4-chloranyl-3-fluoranyl-phenyl)-1-[(3~{R},5~{S})-3,4,5-trimethylpiperazin-1-yl]carbonyl-piperidine-3-carboxamide'>Z1I</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=8gd1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8gd1 OCA], [https://pdbe.org/8gd1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8gd1 RCSB], [https://www.ebi.ac.uk/pdbsum/8gd1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8gd1 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 ability of the HIV-1 accessory proteins Nef and Vpu to decrease CD4 levels contributes to the protection of infected cells from antibody-dependent cellular cytotoxicity (ADCC) by preventing the exposure of Env vulnerable epitopes. Small-molecule CD4 mimetics (CD4mc) based on the indane and piperidine scaffolds such as (+)-BNM-III-170 and (S)-MCG-IV-210 sensitize HIV-1-infected cells to ADCC by exposing CD4-induced (CD4i) epitopes recognized by non-neutralizing antibodies that are abundantly present in plasma from people living with HIV. Here, we characterize a new family of CD4mc, (S)-MCG-IV-210 derivatives, based on the piperidine scaffold which engages the gp120 within the Phe43 cavity by targeting the highly conserved Asp(368) Env residue. We utilized structure-based approaches and developed a series of piperidine analogs with improved activity to inhibit the infection of difficult-to-neutralize tier-2 viruses and sensitize infected cells to ADCC mediated by HIV+ plasma. Moreover, the new analogs formed an H-bond with the alpha-carboxylic acid group of Asp(368), opening a new avenue to enlarge the breadth of this family of anti-Env small molecules. Overall, the new structural and biological attributes of these molecules make them good candidates for strategies aimed at the elimination of HIV-1-infected cells.

Piperidine CD4-Mimetic Compounds Expose Vulnerable Env Epitopes Sensitizing HIV-1-Infected Cells to ADCC.,Ding S, Tolbert WD, Zhu H, Lee D, Marchitto L, Higgins T, Zhao X, Nguyen D, Sherburn R, Richard J, Gendron-Lepage G, Medjahed H, Mohammadi M, Abrams C, Pazgier M, Smith AB 3rd, Finzi A Viruses. 2023 May 17;15(5):1185. doi: 10.3390/v15051185. PMID:37243271<ref>PMID:37243271</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8gd1" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Human immunodeficiency virus 1]]
[[Category: Large Structures]]
[[Category: Nguyen DN]]
[[Category: Pazgier M]]
[[Category: Tolbert WD]]