5u7m - Revision history

OCA at 14:31, 6 November 2017

OCA — Mon, 06 Nov 2017 14:31:48 GMT

←Older revision		Revision as of 14:31, 6 November 2017
Line 1:		Line 1:

-	==Crystal Structure of HIV-1 BG505 SOSIP.664 Prefusion Env Trimer ~~bound~~ to ~~small molecule~~ HIV-1 ~~entry inhibitor~~ BMS-378806 in Complex with Human Antibodies PGT122 and 35O22 at 3.8 A.==	+	==Crystal Structure of HIV-1 BG505 SOSIP.664 Prefusion Env Trimer Bound to Small Molecule HIV-1 Entry Inhibitor BMS-378806 in Complex with Human Antibodies PGT122 and 35O22 at 3.8 Angstrom==
	<StructureSection load='5u7m' size='340' side='right' caption='[[5u7m]], [[Resolution\|resolution]] 3.02Å' scene=''>		<StructureSection load='5u7m' size='340' side='right' caption='[[5u7m]], [[Resolution\|resolution]] 3.02Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5u7m]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U7M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5U7M FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5u7m]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/9hiv1 9hiv1] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U7M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5U7M FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=83G:1-[(2R)-4-(benzenecarbonyl)-2-methylpiperazin-1-yl]-2-(4-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)ethane-1,2-dione'>83G</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=83G:1-[(2R)-4-(benzenecarbonyl)-2-methylpiperazin-1-yl]-2-(4-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)ethane-1,2-dione'>83G</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5u7o\|5u7o]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5u7o\|5u7o]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">env ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 9HIV1])</td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5u7m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u7m OCA], [http://pdbe.org/5u7m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5u7m RCSB], [http://www.ebi.ac.uk/pdbsum/5u7m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5u7m ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5u7m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u7m OCA], [http://pdbe.org/5u7m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5u7m RCSB], [http://www.ebi.ac.uk/pdbsum/5u7m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5u7m ProSAT]</span></td></tr>
	</table>		</table>
Line 23:		Line 24:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Kwong, P D]]		[[Category: Kwong, P D]]
	[[Category: Lai, Y T]]		[[Category: Lai, Y T]]

OCA at 03:51, 6 September 2017

OCA — Wed, 06 Sep 2017 03:51:47 GMT

←Older revision		Revision as of 03:51, 6 September 2017
Line 10:		Line 10:
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/Q2N0S5_9HIV1 Q2N0S5_9HIV1]] The envelope glyprotein gp160 precursor down-modulates cell surface CD4 antigen by interacting with it in the endoplasmic reticulum and blocking its transport to the cell surface.[RuleBase:RU004292][SAAS:SAAS00139820] The gp120-gp41 heterodimer allows rapid transcytosis of the virus through CD4 negative cells such as simple epithelial monolayers of the intestinal, rectal and endocervical epithelial barriers. Both gp120 and gp41 specifically recognize glycosphingolipids galactosyl-ceramide (GalCer) or 3' sulfo-galactosyl-ceramide (GalS) present in the lipid rafts structures of epithelial cells. Binding to these alternative receptors allows the rapid transcytosis of the virus through the epithelial cells. This transcytotic vesicle-mediated transport of virions from the apical side to the basolateral side of the epithelial cells does not involve infection of the cells themselves.[SAAS:SAAS00140087]		[[http://www.uniprot.org/uniprot/Q2N0S5_9HIV1 Q2N0S5_9HIV1]] The envelope glyprotein gp160 precursor down-modulates cell surface CD4 antigen by interacting with it in the endoplasmic reticulum and blocking its transport to the cell surface.[RuleBase:RU004292][SAAS:SAAS00139820] The gp120-gp41 heterodimer allows rapid transcytosis of the virus through CD4 negative cells such as simple epithelial monolayers of the intestinal, rectal and endocervical epithelial barriers. Both gp120 and gp41 specifically recognize glycosphingolipids galactosyl-ceramide (GalCer) or 3' sulfo-galactosyl-ceramide (GalS) present in the lipid rafts structures of epithelial cells. Binding to these alternative receptors allows the rapid transcytosis of the virus through the epithelial cells. This transcytotic vesicle-mediated transport of virions from the apical side to the basolateral side of the epithelial cells does not involve infection of the cells themselves.[SAAS:SAAS00140087]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The HIV-1 envelope (Env) spike is a conformational machine that transitions between prefusion (closed, CD4- and CCR5-bound) and postfusion states to facilitate HIV-1 entry into cells. Although the prefusion closed conformation is a potential target for inhibition, development of small-molecule leads has been stymied by difficulties in obtaining structural information. Here, we report crystal structures at 3.8-A resolution of an HIV-1-Env trimer with BMS-378806 and a derivative BMS-626529 for which a prodrug version is currently in Phase III clinical trials. Both lead candidates recognized an induced binding pocket that was mostly excluded from solvent and comprised of Env elements from a conserved helix and the beta20-21 hairpin. In both structures, the beta20-21 region assumed a conformation distinct from prefusion-closed and CD4-bound states. Together with biophysical and antigenicity characterizations, the structures illuminate the allosteric and competitive mechanisms by which these small-molecule leads inhibit CD4-induced structural changes in Env.
		+
		+	Crystal structures of trimeric HIV envelope with entry inhibitors BMS-378806 and BMS-626529.,Pancera M, Lai YT, Bylund T, Druz A, Narpala S, O'Dell S, Schon A, Bailer RT, Chuang GY, Geng H, Louder MK, Rawi R, Soumana DI, Finzi A, Herschhorn A, Madani N, Sodroski J, Freire E, Langley DR, Mascola JR, McDermott AB, Kwong PD Nat Chem Biol. 2017 Aug 21. doi: 10.1038/nchembio.2460. PMID:28825711<ref>PMID:28825711</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 5u7m" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 14:56, 5 September 2017

OCA — Tue, 05 Sep 2017 14:56:57 GMT

←Older revision		Revision as of 14:56, 5 September 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 5u7m is ON HOLD~~	+	==Crystal Structure of HIV-1 BG505 SOSIP.664 Prefusion Env Trimer bound to small molecule HIV-1 entry inhibitor BMS-378806 in Complex with Human Antibodies PGT122 and 35O22 at 3.8 A.==
-		+	<StructureSection load='5u7m' size='340' side='right' caption='[[5u7m]], [[Resolution\|resolution]] 3.02Å' scene=''>
-	~~Authors: Pancera, M., Lai, Y.-T., Kwong, P.D.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[5u7m]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U7M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5U7M FirstGlance]. <br>
-	~~Description:~~ Crystal Structure of HIV-1 BG505 SOSIP.664 Prefusion Env Trimer bound to small molecule HIV-1 entry inhibitor BMS-378806 in Complex with Human Antibodies PGT122 and 35O22 at 3.8 A.	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=83G:1-[(2R)-4-(benzenecarbonyl)-2-methylpiperazin-1-yl]-2-(4-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)ethane-1,2-dione'>83G</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5u7o\|5u7o]]</td></tr>
-	[[~~Category~~: ~~Lai~~, Y.-T]]	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5u7m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u7m OCA], [http://pdbe.org/5u7m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5u7m RCSB], [http://www.ebi.ac.uk/pdbsum/5u7m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5u7m ProSAT]</span></td></tr>
-	[[Category: Kwong, P.D]]	+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/Q2N0S5_9HIV1 Q2N0S5_9HIV1]] The envelope glyprotein gp160 precursor down-modulates cell surface CD4 antigen by interacting with it in the endoplasmic reticulum and blocking its transport to the cell surface.[RuleBase:RU004292][SAAS:SAAS00139820] The gp120-gp41 heterodimer allows rapid transcytosis of the virus through CD4 negative cells such as simple epithelial monolayers of the intestinal, rectal and endocervical epithelial barriers. Both gp120 and gp41 specifically recognize glycosphingolipids galactosyl-ceramide (GalCer) or 3' sulfo-galactosyl-ceramide (GalS) present in the lipid rafts structures of epithelial cells. Binding to these alternative receptors allows the rapid transcytosis of the virus through the epithelial cells. This transcytotic vesicle-mediated transport of virions from the apical side to the basolateral side of the epithelial cells does not involve infection of the cells themselves.[SAAS:SAAS00140087]
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Kwong, P D]]
		+	[[Category: Lai, Y T]]
	[[Category: Pancera, M]]		[[Category: Pancera, M]]
		+	[[Category: Hiv-1 entry]]
		+	[[Category: Inhibitor]]
		+	[[Category: Small molecule]]
		+	[[Category: Viral protein-immune system complex]]

OCA at 10:19, 4 May 2017

OCA — Thu, 04 May 2017 10:19:58 GMT

←Older revision		Revision as of 10:19, 4 May 2017
Line 5:		Line 5:
	Authors: Pancera, M., Lai, Y.-T., Kwong, P.D.		Authors: Pancera, M., Lai, Y.-T., Kwong, P.D.

-	Description: Crystal Structure of HIV-1 BG505 SOSIP.664 Prefusion Env Trimer bound to small molecule HIV-1 entry inhibitor BMS-378806 in Complex with Human Antibodies PGT122 and 35O22.	+	Description: Crystal Structure of HIV-1 BG505 SOSIP.664 Prefusion Env Trimer bound to small molecule HIV-1 entry inhibitor BMS-378806 in Complex with Human Antibodies PGT122 and 35O22 at 3.8 A.
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Lai, Y.-T]]		[[Category: Lai, Y.-T]]
	[[Category: Kwong, P.D]]		[[Category: Kwong, P.D]]
	[[Category: Pancera, M]]		[[Category: Pancera, M]]

OCA at 15:09, 2 January 2017

OCA — Mon, 02 Jan 2017 15:09:36 GMT

←Older revision		Revision as of 15:09, 2 January 2017
Line 3:		Line 3:
	The entry 5u7m is ON HOLD		The entry 5u7m is ON HOLD

-	Authors: Pancera, M, Lai, Y-T, Kwong, P.D.	+	Authors: Pancera, M., Lai, Y.-T., Kwong, P.D.

	Description: Crystal Structure of HIV-1 BG505 SOSIP.664 Prefusion Env Trimer bound to small molecule HIV-1 entry inhibitor BMS-378806 in Complex with Human Antibodies PGT122 and 35O22.		Description: Crystal Structure of HIV-1 BG505 SOSIP.664 Prefusion Env Trimer bound to small molecule HIV-1 entry inhibitor BMS-378806 in Complex with Human Antibodies PGT122 and 35O22.
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: ~~Pancera, M,~~ Lai, Y-T, Kwong, P.D]]	+	[[Category: Lai, Y.-T]]
		+	[[Category: Kwong, P.D]]
		+	[[Category: Pancera, M]]

OCA: Protected "5u7m" [edit=sysop:move=sysop]

OCA — Thu, 22 Dec 2016 20:30:15 GMT

Protected "5u7m" [edit=sysop:move=sysop]

←Older revision

Revision as of 20:30, 22 December 2016

OCA: New page: '''Unreleased structure''' The entry 5u7m is ON HOLD Authors: Pancera, M, Lai, Y-T, Kwong, P.D. Description: Crystal Structure of HIV-1 BG505 SOSIP.664 Prefusion Env Trimer bound to sm...

OCA — Thu, 22 Dec 2016 20:30:13 GMT

New page: '''Unreleased structure''' The entry 5u7m is ON HOLD Authors: Pancera, M, Lai, Y-T, Kwong, P.D. Description: Crystal Structure of HIV-1 BG505 SOSIP.664 Prefusion Env Trimer bound to sm...

New page

'''Unreleased structure'''

The entry 5u7m is ON HOLD

Authors: Pancera, M, Lai, Y-T, Kwong, P.D.

Description: Crystal Structure of HIV-1 BG505 SOSIP.664 Prefusion Env Trimer bound to small molecule HIV-1 entry inhibitor BMS-378806 in Complex with Human Antibodies PGT122 and 35O22.
[[Category: Unreleased Structures]]
[[Category: Pancera, M, Lai, Y-T, Kwong, P.D]]