7quo - Revision history

OCA at 07:58, 7 February 2024

OCA — Wed, 07 Feb 2024 07:58:47 GMT

←Older revision		Revision as of 07:58, 7 February 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7quo]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_BL21(DE3) Escherichia coli BL21(DE3)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7QUO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QUO FirstGlance]. <br>		<table><tr><td colspan='2'>[[7quo]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_BL21(DE3) Escherichia coli BL21(DE3)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7QUO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QUO FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 3Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=7quo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7quo OCA], [https://pdbe.org/7quo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7quo RCSB], [https://www.ebi.ac.uk/pdbsum/7quo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7quo 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=7quo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7quo OCA], [https://pdbe.org/7quo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7quo RCSB], [https://www.ebi.ac.uk/pdbsum/7quo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7quo ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/Q9S497_ECOLX Q9S497_ECOLX]		[https://www.uniprot.org/uniprot/Q9S497_ECOLX Q9S497_ECOLX]
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	BACKGROUND: Escherichia coli strains adhere to the normally sterile human uroepithelium using type 1 pili, that are long, hairy surface organelles exposing a mannose-binding FimH adhesin at the tip. A small percentage of adhered bacteria can successfully invade bladder cells, presumably via pathways mediated by the high-mannosylated uroplakin-Ia and alpha3beta1 integrins found throughout the uroepithelium. Invaded bacteria replicate and mature into dense, biofilm-like inclusions in preparation of fluxing and of infection of neighbouring cells, being the major cause of the troublesome recurrent urinary tract infections. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrate that alpha-D-mannose based inhibitors of FimH not only block bacterial adhesion on uroepithelial cells but also antagonize invasion and biofilm formation. Heptyl alpha-D-mannose prevents binding of type 1-piliated E. coli to the human bladder cell line 5637 and reduces both adhesion and invasion of the UTI89 cystitis isolate instilled in mouse bladder via catheterization. Heptyl alpha-D-mannose also specifically inhibited biofilm formation at micromolar concentrations. The structural basis of the great inhibitory potential of alkyl and aryl alpha-D-mannosides was elucidated in the crystal structure of the FimH receptor-binding domain in complex with oligomannose-3. FimH interacts with Man alpha1,3Man beta1,4GlcNAc beta1,4GlcNAc in an extended binding site. The interactions along the alpha1,3 glycosidic bond and the first beta1,4 linkage to the chitobiose unit are conserved with those of FimH with butyl alpha-D-mannose. The strong stacking of the central mannose with the aromatic ring of Tyr48 is congruent with the high affinity found for synthetic inhibitors in which this mannose is substituted for by an aromatic group. CONCLUSIONS/SIGNIFICANCE: The potential of ligand-based design of antagonists of urinary tract infections is ruled by the structural mimicry of natural epitopes and extends into blocking of bacterial invasion, intracellular growth and capacity to fluxing and of recurrence of the infection.
-
-	Intervening with urinary tract infections using anti-adhesives based on the crystal structure of the FimH-oligomannose-3 complex.,Wellens A, Garofalo C, Nguyen H, Van Gerven N, Slattegard R, Hernalsteens JP, Wyns L, Oscarson S, De Greve H, Hultgren S, Bouckaert J PLoS One. 2008 Apr 30;3(4):e2040. PMID:18446213<ref>PMID:18446213</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 7quo" style="background-color:#fffaf0;"></div>
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 11:13, 1 February 2023

OCA — Wed, 01 Feb 2023 11:13:50 GMT

←Older revision		Revision as of 11:13, 1 February 2023
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7quo is ~~ON HOLD until Paper~~ Publication	+	==FimH lectin domain in complex with oligomannose-6==
		+	<StructureSection load='7quo' size='340' side='right'caption='[[7quo]], [[Resolution\|resolution]] 3.00Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[7quo]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_BL21(DE3) Escherichia coli BL21(DE3)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7QUO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QUO FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=7quo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7quo OCA], [https://pdbe.org/7quo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7quo RCSB], [https://www.ebi.ac.uk/pdbsum/7quo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7quo ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/Q9S497_ECOLX Q9S497_ECOLX]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	BACKGROUND: Escherichia coli strains adhere to the normally sterile human uroepithelium using type 1 pili, that are long, hairy surface organelles exposing a mannose-binding FimH adhesin at the tip. A small percentage of adhered bacteria can successfully invade bladder cells, presumably via pathways mediated by the high-mannosylated uroplakin-Ia and alpha3beta1 integrins found throughout the uroepithelium. Invaded bacteria replicate and mature into dense, biofilm-like inclusions in preparation of fluxing and of infection of neighbouring cells, being the major cause of the troublesome recurrent urinary tract infections. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrate that alpha-D-mannose based inhibitors of FimH not only block bacterial adhesion on uroepithelial cells but also antagonize invasion and biofilm formation. Heptyl alpha-D-mannose prevents binding of type 1-piliated E. coli to the human bladder cell line 5637 and reduces both adhesion and invasion of the UTI89 cystitis isolate instilled in mouse bladder via catheterization. Heptyl alpha-D-mannose also specifically inhibited biofilm formation at micromolar concentrations. The structural basis of the great inhibitory potential of alkyl and aryl alpha-D-mannosides was elucidated in the crystal structure of the FimH receptor-binding domain in complex with oligomannose-3. FimH interacts with Man alpha1,3Man beta1,4GlcNAc beta1,4GlcNAc in an extended binding site. The interactions along the alpha1,3 glycosidic bond and the first beta1,4 linkage to the chitobiose unit are conserved with those of FimH with butyl alpha-D-mannose. The strong stacking of the central mannose with the aromatic ring of Tyr48 is congruent with the high affinity found for synthetic inhibitors in which this mannose is substituted for by an aromatic group. CONCLUSIONS/SIGNIFICANCE: The potential of ligand-based design of antagonists of urinary tract infections is ruled by the structural mimicry of natural epitopes and extends into blocking of bacterial invasion, intracellular growth and capacity to fluxing and of recurrence of the infection.

-	~~Authors: Bouckaert, J~~., ~~Bourenkov~~, G.P.	+	Intervening with urinary tract infections using anti-adhesives based on the crystal structure of the FimH-oligomannose-3 complex.,Wellens A, Garofalo C, Nguyen H, Van Gerven N, Slattegard R, Hernalsteens JP, Wyns L, Oscarson S, De Greve H, Hultgren S, Bouckaert J PLoS One. 2008 Apr 30;3(4):e2040. PMID:18446213<ref>PMID:18446213</ref>

-	~~Description: FimH lectin domain in complex with oligomannose~~-6	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: Bouckaert, J]]	+	<div class="pdbe-citations 7quo" style="background-color:#fffaf0;"></div>
-	[[Category: Bourenkov~~, G.P~~]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Bouckaert J]]
		+	[[Category: Bourenkov GP]]

OCA at 04:42, 25 January 2023

OCA — Wed, 25 Jan 2023 04:42:38 GMT

←Older revision		Revision as of 04:42, 25 January 2023
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Bouckaert, J., Bourenkov, G.P.		Authors: Bouckaert, J., Bourenkov, G.P.

OCA at 08:14, 30 November 2022

OCA — Wed, 30 Nov 2022 08:14:08 GMT

←Older revision		Revision as of 08:14, 30 November 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7quo is ON HOLD ~~until Paper Publication~~	+	The entry 7quo is ON HOLD

	Authors: Bouckaert, J., Bourenkov, G.P.		Authors: Bouckaert, J., Bourenkov, G.P.
Line 7:		Line 7:
	Description: FimH lectin domain in complex with oligomannose-6		Description: FimH lectin domain in complex with oligomannose-6
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Bourenkov, G.P]]
	[[Category: Bouckaert, J]]		[[Category: Bouckaert, J]]
		+	[[Category: Bourenkov, G.P]]

OCA at 03:49, 15 June 2022

OCA — Wed, 15 Jun 2022 03:49:43 GMT

←Older revision		Revision as of 03:49, 15 June 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Bouckaert, J., Bourenkov, G.P.		Authors: Bouckaert, J., Bourenkov, G.P.

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

OCA — Thu, 27 Jan 2022 05:23:49 GMT

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

←Older revision

Revision as of 05:23, 27 January 2022

OCA: New page: '''Unreleased structure''' The entry 7quo is ON HOLD Authors: Bouckaert, J., Bourenkov, G.P. Description: FimH lectin domain in complex with oligomannose-6 [[Category: Unreleased Struc...

OCA — Thu, 27 Jan 2022 05:23:47 GMT

New page: '''Unreleased structure''' The entry 7quo is ON HOLD Authors: Bouckaert, J., Bourenkov, G.P. Description: FimH lectin domain in complex with oligomannose-6 [[Category: Unreleased Struc...

New page

'''Unreleased structure'''

The entry 7quo is ON HOLD

Authors: Bouckaert, J., Bourenkov, G.P.

Description: FimH lectin domain in complex with oligomannose-6
[[Category: Unreleased Structures]]
[[Category: Bourenkov, G.P]]
[[Category: Bouckaert, J]]