7b69 - Revision history

OCA at 12:22, 1 February 2024

2024-02-01T12:22:30Z

←Older revision		Revision as of 12:22, 1 February 2024
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7b69]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_polyomavirus_1 Human polyomavirus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7B69 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7B69 FirstGlance]. <br>		<table><tr><td colspan='2'>[[7b69]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_polyomavirus_1 Human polyomavirus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7B69 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7B69 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.474Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</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=7b69 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7b69 OCA], [https://pdbe.org/7b69 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7b69 RCSB], [https://www.ebi.ac.uk/pdbsum/7b69 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7b69 ProSAT]</span></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=7b69 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7b69 OCA], [https://pdbe.org/7b69 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7b69 RCSB], [https://www.ebi.ac.uk/pdbsum/7b69 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7b69 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/VP1_POVBK VP1_POVBK]] Forms an icosahedral capsid with a T=7 symmetry and a 50 nm diameter. The capsid is composed of 72 pentamers linked to each other by disulfide bonds and associated with VP2 or VP3 proteins. Interacts with gangliosides GT1b and GD1b containing terminal alpha(2-8)-linked sialic acids on the cell surface to provide virion attachment to target cell. This attachment induces virion internalization predominantly through caveolin-mediated endocytosis and traffics to the endoplasmic reticulum. Inside the endoplasmic reticulum, the protein folding machinery isomerizes VP1 interpentamer disulfide bonds, thereby triggering initial uncoating. Next, the virion uses the endoplasmic reticulum-associated degradation machinery to probably translocate in the cytosol before reaching the nucleus. Nuclear entry of the viral DNA involves the selective exposure and importin recognition of VP2/Vp3 nuclear localization signal. In late phase of infection, neo-synthesized VP1 encapsulates replicated genomic DNA in the nucleus, and participates in rearranging nucleosomes around the viral DNA (By similarity).<ref>PMID:15479799</ref> <ref>PMID:16415013</ref>	+	[https://www.uniprot.org/uniprot/VP1_POVBK VP1_POVBK] Forms an icosahedral capsid with a T=7 symmetry and a 50 nm diameter. The capsid is composed of 72 pentamers linked to each other by disulfide bonds and associated with VP2 or VP3 proteins. Interacts with gangliosides GT1b and GD1b containing terminal alpha(2-8)-linked sialic acids on the cell surface to provide virion attachment to target cell. This attachment induces virion internalization predominantly through caveolin-mediated endocytosis and traffics to the endoplasmic reticulum. Inside the endoplasmic reticulum, the protein folding machinery isomerizes VP1 interpentamer disulfide bonds, thereby triggering initial uncoating. Next, the virion uses the endoplasmic reticulum-associated degradation machinery to probably translocate in the cytosol before reaching the nucleus. Nuclear entry of the viral DNA involves the selective exposure and importin recognition of VP2/Vp3 nuclear localization signal. In late phase of infection, neo-synthesized VP1 encapsulates replicated genomic DNA in the nucleus, and participates in rearranging nucleosomes around the viral DNA (By similarity).<ref>PMID:15479799</ref> <ref>PMID:16415013</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 19:43, 7 September 2022

2022-09-07T19:43:05Z

←Older revision		Revision as of 19:43, 7 September 2022
Line 3:		Line 3:
	<StructureSection load='7b69' size='340' side='right'caption='[[7b69]], [[Resolution\|resolution]] 1.47Å' scene=''>		<StructureSection load='7b69' size='340' side='right'caption='[[7b69]], [[Resolution\|resolution]] 1.47Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7b69]] is a 10 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7B69 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7B69 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7b69]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_polyomavirus_1 Human polyomavirus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7B69 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7B69 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</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=7b69 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7b69 OCA], [https://pdbe.org/7b69 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7b69 RCSB], [https://www.ebi.ac.uk/pdbsum/7b69 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7b69 ProSAT]</span></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=7b69 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7b69 OCA], [https://pdbe.org/7b69 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7b69 RCSB], [https://www.ebi.ac.uk/pdbsum/7b69 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7b69 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/VP1_POVBK VP1_POVBK]] Forms an icosahedral capsid with a T=7 symmetry and a 50 nm diameter. The capsid is composed of 72 pentamers linked to each other by disulfide bonds and associated with VP2 or VP3 proteins. Interacts with gangliosides GT1b and GD1b containing terminal alpha(2-8)-linked sialic acids on the cell surface to provide virion attachment to target cell. This attachment induces virion internalization predominantly through caveolin-mediated endocytosis and traffics to the endoplasmic reticulum. Inside the endoplasmic reticulum, the protein folding machinery isomerizes VP1 interpentamer disulfide bonds, thereby triggering initial uncoating. Next, the virion uses the endoplasmic reticulum-associated degradation machinery to probably translocate in the cytosol before reaching the nucleus. Nuclear entry of the viral DNA involves the selective exposure and importin recognition of VP2/Vp3 nuclear localization signal. In late phase of infection, neo-synthesized VP1 encapsulates replicated genomic DNA in the nucleus, and participates in rearranging nucleosomes around the viral DNA (By similarity).<ref>PMID:15479799</ref> <ref>PMID:16415013</ref>	+	[[https://www.uniprot.org/uniprot/VP1_POVBK VP1_POVBK]] Forms an icosahedral capsid with a T=7 symmetry and a 50 nm diameter. The capsid is composed of 72 pentamers linked to each other by disulfide bonds and associated with VP2 or VP3 proteins. Interacts with gangliosides GT1b and GD1b containing terminal alpha(2-8)-linked sialic acids on the cell surface to provide virion attachment to target cell. This attachment induces virion internalization predominantly through caveolin-mediated endocytosis and traffics to the endoplasmic reticulum. Inside the endoplasmic reticulum, the protein folding machinery isomerizes VP1 interpentamer disulfide bonds, thereby triggering initial uncoating. Next, the virion uses the endoplasmic reticulum-associated degradation machinery to probably translocate in the cytosol before reaching the nucleus. Nuclear entry of the viral DNA involves the selective exposure and importin recognition of VP2/Vp3 nuclear localization signal. In late phase of infection, neo-synthesized VP1 encapsulates replicated genomic DNA in the nucleus, and participates in rearranging nucleosomes around the viral DNA (By similarity).<ref>PMID:15479799</ref> <ref>PMID:16415013</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 22:		Line 22:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human polyomavirus 1]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Beelen, S]]	+	[[Category: Beelen S]]
-	[[Category: Osipov~~, E M~~]]	+	[[Category: Osipov EM]]
-	[[Category: Strelkov~~, S V]]~~	+	[[Category: Strelkov SV]]
-	~~[[Category: Capsid protein]]~~	+
-	~~[[Category: Polyomavirus]]~~	+
-	~~[[Category: Viral protein~~]]	+

OCA at 06:41, 31 August 2022

2022-08-31T06:41:27Z

←Older revision		Revision as of 06:41, 31 August 2022
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	==BK Polyomavirus VP1 pentamer core(residues 26-299) mutant C104S==		==BK Polyomavirus VP1 pentamer core(residues 26-299) mutant C104S==
-	<StructureSection load='7b69' size='340' side='right'caption='[[7b69]]' scene=''>	+	<StructureSection load='7b69' size='340' side='right'caption='[[7b69]], [[Resolution\|resolution]] 1.47Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7B69 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7B69 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7b69]] is a 10 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7B69 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7B69 FirstGlance]. <br>
-	</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=7b69 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7b69 OCA], [https://pdbe.org/7b69 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7b69 RCSB], [https://www.ebi.ac.uk/pdbsum/7b69 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7b69 ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</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=7b69 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7b69 OCA], [https://pdbe.org/7b69 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7b69 RCSB], [https://www.ebi.ac.uk/pdbsum/7b69 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7b69 ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/VP1_POVBK VP1_POVBK]] Forms an icosahedral capsid with a T=7 symmetry and a 50 nm diameter. The capsid is composed of 72 pentamers linked to each other by disulfide bonds and associated with VP2 or VP3 proteins. Interacts with gangliosides GT1b and GD1b containing terminal alpha(2-8)-linked sialic acids on the cell surface to provide virion attachment to target cell. This attachment induces virion internalization predominantly through caveolin-mediated endocytosis and traffics to the endoplasmic reticulum. Inside the endoplasmic reticulum, the protein folding machinery isomerizes VP1 interpentamer disulfide bonds, thereby triggering initial uncoating. Next, the virion uses the endoplasmic reticulum-associated degradation machinery to probably translocate in the cytosol before reaching the nucleus. Nuclear entry of the viral DNA involves the selective exposure and importin recognition of VP2/Vp3 nuclear localization signal. In late phase of infection, neo-synthesized VP1 encapsulates replicated genomic DNA in the nucleus, and participates in rearranging nucleosomes around the viral DNA (By similarity).<ref>PMID:15479799</ref> <ref>PMID:16415013</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Polyomaviruses are a family of ubiquitous double-stranded DNA viruses many of which are human pathogens. These include BK polyomavirus which causes severe urinary tract infection in immunocompromised patients and Merkel cell polyomavirus associated with aggressive cancers. The small genome of polyomaviruses lacks conventional drug targets, and no specific drugs are available at present. Here we focus on the main structural protein VP1 of BK polyomavirus which is responsible for icosahedral capsid formation. To provide a foundation towards rational drug design, we crystallized truncated VP1 pentamers and subjected them to a high-throughput screening for binding drug-like fragments through a direct X-ray analysis. To enable a highly performant screening, rigorous optimization of the crystallographic pipeline and processing with the latest generation PanDDA2 software were necessary. As a result, a total of 144 binding hits were established. Importantly, the hits are well clustered in six surface pockets. Three pockets are located on the outside of the pentamer and map on the regions where the 'invading' C-terminal arm of another pentamer is attached upon capsid assembly. Another set of three pockets is situated within the wide pore along the five-fold axis of the VP1 pentamer. These pockets are situated at the interaction interface with the minor capsid protein VP2 which is indispensable for normal functioning of the virus. Here we systematically analyse the three outside pockets which are highly conserved across various polyomaviruses, while point mutations in these pockets are detrimental for viral replication. We show that one of the pockets can accommodate antipsychotic drug trifluoperazine. For each pocket, we derive pharmacophore features which enable the design of small molecules preventing the interaction between VP1 pentamers and therefore inhibiting capsid assembly. Our data lay a foundation towards a rational development of first-in-class drugs targeting polyomavirus capsid.
		+
		+	Discovery of novel druggable pockets on polyomavirus VP1 through crystallographic fragment-based screening to develop capsid assembly inhibitors.,Osipov EM, Munawar AH, Beelen S, Fearon D, Douangamath A, Wild C, Weeks SD, Van Aerschot A, von Delft F, Strelkov SV RSC Chem Biol. 2022 Apr 29;3(8):1013-1027. doi: 10.1039/d2cb00052k. eCollection, 2022 Aug 3. PMID:35974998<ref>PMID:35974998</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7b69" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Beelen S]]	+	[[Category: Beelen, S]]
-	[[Category: Osipov EM]]	+	[[Category: Osipov, E M]]
-	[[Category: Strelkov SV]]	+	[[Category: Strelkov, S V]]
		+	[[Category: Capsid protein]]
		+	[[Category: Polyomavirus]]
		+	[[Category: Viral protein]]

OCA at 09:42, 22 June 2022

2022-06-22T09:42:32Z

←Older revision		Revision as of 09:42, 22 June 2022
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7b69 is ~~ON HOLD until Paper Publication~~	+	==BK Polyomavirus VP1 pentamer core(residues 26-299) mutant C104S==
-		+	<StructureSection load='7b69' size='340' side='right'caption='[[7b69]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7B69 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7B69 FirstGlance]. <br>
-	~~Description~~:	+	</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=7b69 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7b69 OCA], [https://pdbe.org/7b69 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7b69 RCSB], [https://www.ebi.ac.uk/pdbsum/7b69 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7b69 ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Beelen S]]
		+	[[Category: Osipov EM]]
		+	[[Category: Strelkov SV]]

OCA at 05:05, 10 November 2021

2021-11-10T05:05:18Z

←Older revision		Revision as of 05:05, 10 November 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7b69 is ON HOLD	+	The entry 7b69 is ON HOLD until Paper Publication

	Authors:		Authors:

OCA at 07:30, 29 September 2021

2021-09-29T07:30:45Z

←Older revision		Revision as of 07:30, 29 September 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7b69 is ON HOLD ~~until sometime in the future~~	+	The entry 7b69 is ON HOLD

	Authors:		Authors:

OCA at 05:23, 22 September 2021

2021-09-22T05:23:17Z

←Older revision		Revision as of 05:23, 22 September 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7b69 is ON HOLD until ~~Paper Publication~~	+	The entry 7b69 is ON HOLD until sometime in the future

	Authors:		Authors:

OCA at 05:30, 6 January 2021

2021-01-06T05:30:42Z

←Older revision		Revision as of 05:30, 6 January 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7b69 is ON HOLD	+	The entry 7b69 is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "7b69" [edit=sysop:move=sysop]

2020-12-16T10:59:17Z

Protected "7b69" [edit=sysop:move=sysop]

←Older revision

Revision as of 10:59, 16 December 2020

OCA: New page: '''Unreleased structure''' The entry 7b69 is ON HOLD Authors: Description: Category: Unreleased Structures

2020-12-16T10:59:16Z

New page: '''Unreleased structure''' The entry 7b69 is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7b69 is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]