OCA at 06:31, 7 April 2023

2023-04-07T06:31:10Z

←Older revision		Revision as of 06:31, 7 April 2023
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-	'''Unreleased structure'''

-	~~The entry~~ 8flz is ~~ON HOLD until Paper~~ Publication	+	==HIV-1 gp120 complex with CJF-III-049-S==
		+	<StructureSection load='8flz' size='340' side='right'caption='[[8flz]], [[Resolution\|resolution]] 2.00Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8flz]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/HIV-1_06TG.HT008 HIV-1 06TG.HT008]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8FLZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8FLZ FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7IT:N~1~-{(1R,2R,3S)-2-(carbamimidamidomethyl)-3-[(3S)-3,4-dihydroxybutyl]-5-[(methylamino)methyl]-2,3-dihydro-1H-inden-1-yl}-N~2~-(4-chloro-3-fluorophenyl)ethanediamide'>7IT</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=8flz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8flz OCA], [https://pdbe.org/8flz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8flz RCSB], [https://www.ebi.ac.uk/pdbsum/8flz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8flz ProSAT]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Binding to the host cell receptors, CD4 and CCR5/CXCR4, triggers large-scale conformational changes in the HIV-1 envelope glycoprotein (Env) trimer [(gp120/gp41)(3)] that promote virus entry into the cell. CD4-mimetic compounds (CD4mcs) comprise small organic molecules that bind in the highly conserved CD4-binding site of gp120 and prematurely induce inactivating Env conformational changes, including shedding of gp120 from the Env trimer. By inducing more "open," antibody-susceptible Env conformations, CD4mcs also sensitize HIV-1 virions to neutralization by antibodies and infected cells to antibody-dependent cellular cytotoxicity (ADCC). Here, we report the design, synthesis, and evaluation of novel CD4mcs based on an indoline scaffold. Compared with our current lead indane scaffold CD4mc, BNM-III-170, several indoline CD4mcs exhibit increased potency and breadth against HIV-1 variants from different geographic clades. Viruses that were selected for resistance to the lead indane CD4mc, BNM-III-170, are susceptible to inhibition by the indoline CD4mcs. The indoline CD4mcs also potently sensitize HIV-1-infected cells to ADCC mediated by plasma from HIV-1-infected individuals. Crystal structures indicate that the indoline CD4mcs gain potency compared to the indane CD4mcs through more favorable pi-pi overlap from the indoline pose and by making favorable contacts with the vestibule of the CD4-binding pocket on gp120. The rational design of indoline CD4mcs thus holds promise for further improvements in antiviral activity, potentially contributing to efforts to treat and prevent HIV-1 infection.

-	~~Authors: Gong~~, Z., Hendrickson, W.A.	+	Indoline CD4-mimetic compounds mediate potent and broad HIV-1 inhibition and sensitization to antibody-dependent cellular cytotoxicity.,Fritschi CJ, Anang S, Gong Z, Mohammadi M, Richard J, Bourassa C, Severino KT, Richter H, Yang D, Chen HC, Chiu TJ, Seaman MS, Madani N, Abrams C, Finzi A, Hendrickson WA, Sodroski JG, Smith AB 3rd Proc Natl Acad Sci U S A. 2023 Mar 28;120(13):e2222073120. doi: , 10.1073/pnas.2222073120. Epub 2023 Mar 24. PMID:36961924<ref>PMID:36961924</ref>

-	~~Description~~: HIV-1 ~~gp120 complex with CJF-III-049-S~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: Gong, Z]]	+	<div class="pdbe-citations 8flz" style="background-color:#fffaf0;"></div>
-	[[Category: Hendrickson~~, W.A~~]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: HIV-1 06TG HT008]]
		+	[[Category: Large Structures]]
		+	[[Category: Gong Z]]
		+	[[Category: Hendrickson WA]]

OCA at 09:21, 1 February 2023

2023-02-01T09:21:59Z

←Older revision		Revision as of 09:21, 1 February 2023
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8flz is ON HOLD	+	The entry 8flz is ON HOLD until Paper Publication

	Authors: Gong, Z., Hendrickson, W.A.		Authors: Gong, Z., Hendrickson, W.A.

OCA: Protected "8flz" [edit=sysop:move=sysop]

2022-12-28T06:13:08Z

Protected "8flz" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:13, 28 December 2022

OCA: New page: '''Unreleased structure''' The entry 8flz is ON HOLD Authors: Gong, Z., Hendrickson, W.A. Description: HIV-1 gp120 complex with CJF-III-049-S Category: Unreleased Structures [[Cate...

2022-12-28T06:13:06Z

New page: '''Unreleased structure''' The entry 8flz is ON HOLD Authors: Gong, Z., Hendrickson, W.A. Description: HIV-1 gp120 complex with CJF-III-049-S Category: Unreleased Structures [[Cate...

New page

'''Unreleased structure'''

The entry 8flz is ON HOLD

Authors: Gong, Z., Hendrickson, W.A.

Description: HIV-1 gp120 complex with CJF-III-049-S
[[Category: Unreleased Structures]]
[[Category: Gong, Z]]
[[Category: Hendrickson, W.A]]

8flz - Revision history

OCA at 06:31, 7 April 2023

OCA at 09:21, 1 February 2023

OCA: Protected "8flz" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 8flz is ON HOLD Authors: Gong, Z., Hendrickson, W.A. Description: HIV-1 gp120 complex with CJF-III-049-S Category: Unreleased Structures [[Cate...