9bxd: Difference between revisions

(One intermediate revision by the same user not shown)

Line 1:

~~'''Unreleased structure'''~~

~~The entry~~ 9bxd is ~~ON HOLD~~

==CRYSTAL STRUCTURE OF HIV-1 LM/HS CLADE A/E CRF01 GP120 CORE IN COMPLEX WITH HZ-IV-188==

== Structural highlights ==

<table><tr><td colspan='2'>[[9bxd]] 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=9BXD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9BXD 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]] 1.85Å</td></tr>

<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1ATK:(3S)-1-(4-L-arginylpiperazine-1-carbonyl)-N-(4-chloro-3-fluorophenyl)piperidine-3-carboxamide'>A1ATK</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</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=9bxd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9bxd OCA], [https://pdbe.org/9bxd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9bxd RCSB], [https://www.ebi.ac.uk/pdbsum/9bxd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9bxd ProSAT]</span></td></tr>

</table>

== Function ==

[https://www.uniprot.org/uniprot/A0A0M3KKW9_HV1 A0A0M3KKW9_HV1]

== 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.

~~Authors:~~ Niu, L., Tolbert, W.D., ~~Pazgier, M~~.

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>

~~Description: CRYSTAL STRUCTURE OF HIV-1 LM~~/~~HS CLADE A~~/~~E CRF01 GP120 CORE IN COMPLEX WITH HZ~~-IV-~~188~~

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

[[Category: ~~Unreleased Structures~~]]

</div>

[[Category: ~~Tolbert, W.D~~]]

[[Category: Niu, L]]

== References ==

[[Category: Pazgier, M]]

__TOC__

</StructureSection>

[[Category: Human immunodeficiency virus 1]]

[[Category: Large Structures]]

[[Category: Niu L]]

[[Category: Pazgier M]]

[[Category: Tolbert WD]]

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 9bxd is ON HOLD
+==CRYSTAL STRUCTURE OF HIV-1 LM/HS CLADE A/E CRF01 GP120 CORE IN COMPLEX WITH HZ-IV-188==
+<StructureSection load='9bxd' size='340' side='right'caption='[[9bxd]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[9bxd]] 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=9BXD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9BXD 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]] 1.85&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1ATK:(3S)-1-(4-L-arginylpiperazine-1-carbonyl)-N-(4-chloro-3-fluorophenyl)piperidine-3-carboxamide'>A1ATK</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</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=9bxd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9bxd OCA], [https://pdbe.org/9bxd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9bxd RCSB], [https://www.ebi.ac.uk/pdbsum/9bxd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9bxd 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.
-Authors: Niu, L., Tolbert, W.D., Pazgier, M.
+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>
-Description: CRYSTAL STRUCTURE OF HIV-1 LM/HS CLADE A/E CRF01 GP120 CORE IN COMPLEX WITH HZ-IV-188
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Tolbert, W.D]]
+<div class="pdbe-citations 9bxd" style="background-color:#fffaf0;"></div>
-[[Category: Niu, L]]
+== References ==
-[[Category: Pazgier, M]]
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Human immunodeficiency virus 1]]
+[[Category: Large Structures]]
+[[Category: Niu L]]
+[[Category: Pazgier M]]
+[[Category: Tolbert WD]]