8gd5: Difference between revisions

Revision as of 05:41, 7 June 2023

Crystal Structure of HIV-1 LM/HT Clade A/E CRF01 GP120 Core in Complex with DL-I-102

Structural highlights

8gd5 is a 1 chain structure with sequence from Human immunodeficiency virus 1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	EPE, NAG, Z2O
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

A0A0M3KKW9_9HIV1

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ 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. Piperidine CD4-Mimetic Compounds Expose Vulnerable Env Epitopes Sensitizing HIV-1-Infected Cells to ADCC. Viruses. 2023 May 17;15(5):1185. PMID:37243271 doi:10.3390/v15051185

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] 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. Piperidine CD4-Mimetic Compounds Expose Vulnerable Env Epitopes Sensitizing HIV-1-Infected Cells to ADCC. Viruses. 2023 May 17;15(5):1185. PMID:37243271 doi:10.3390/v15051185

[1]

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8gd5 is ON HOLD  until Paper Publication
+==Crystal Structure of HIV-1 LM/HT Clade A/E CRF01 GP120 Core in Complex with DL-I-102==
+<StructureSection load='8gd5' size='340' side='right'caption='[[8gd5]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8gd5]] 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=8GD5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8GD5 FirstGlance]. <br>
+</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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=Z2O:{4-[(3S,5R)-3-[(4-chloro-3-fluorophenyl)carbamoyl]-5-(hydroxymethyl)piperidine-1-carbonyl]piperazin-1-yl}acetic+acid'>Z2O</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=8gd5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8gd5 OCA], [https://pdbe.org/8gd5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8gd5 RCSB], [https://www.ebi.ac.uk/pdbsum/8gd5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8gd5 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.
-Authors: Tolbert, W.D., Nguyen, D.N., Pazgier, M.
+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>
-Description: Crystal Structure of HIV-1 LM/HT Clade A/E CRF01 GP120 Core in Complex with DL-I-102
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Pazgier, M]]
+<div class="pdbe-citations 8gd5" style="background-color:#fffaf0;"></div>
-[[Category: Tolbert, W.D]]
+== References ==
-[[Category: Nguyen, D.N]]
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Human immunodeficiency virus 1]]
+[[Category: Large Structures]]
+[[Category: Nguyen DN]]
+[[Category: Pazgier M]]
+[[Category: Tolbert WD]]

8gd5: Difference between revisions

Revision as of 05:41, 7 June 2023

Crystal Structure of HIV-1 LM/HT Clade A/E CRF01 GP120 Core in Complex with DL-I-102

Structural highlights

Function

Publication Abstract from PubMed

References

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