OCA at 17:16, 29 November 2023

2023-11-29T17:16:31Z

←Older revision		Revision as of 17:16, 29 November 2023
Line 1:		Line 1:

	==LecA from Pseudomonas aeruginosa in complex with a synthetic monovalent galactosidic inhibitor==		==LecA from Pseudomonas aeruginosa in complex with a synthetic monovalent galactosidic inhibitor==
-	<StructureSection load='7fio' size='340' side='right'caption='[[7fio]]' scene=''>	+	<StructureSection load='7fio' size='340' side='right'caption='[[7fio]], [[Resolution\|resolution]] 1.50Å' 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=7FIO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7FIO FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7fio]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7FIO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7FIO 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=7fio FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7fio OCA], [https://pdbe.org/7fio PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7fio RCSB], [https://www.ebi.ac.uk/pdbsum/7fio PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7fio ProSAT]</span></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]] 1.5Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4VH:N-[2-[4-[(2S)-3-(2-hydroxyethylamino)-3-oxidanylidene-2-(2-phenoxyethanoylamino)propyl]-1,2,3-triazol-1-yl]ethyl]-4-[(2S,3R,4S,5R,6R)-6-(hydroxymethyl)-3,4,5-tris(oxidanyl)oxan-2-yl]sulfanyl-benzamide'>4VH</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=7fio FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7fio OCA], [https://pdbe.org/7fio PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7fio RCSB], [https://www.ebi.ac.uk/pdbsum/7fio PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7fio ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/PA1L_PSEAE PA1L_PSEAE] D-galactose specific lectin. Binds in decreasing order of affinity: melibiose, methyl-alpha-D-galactoside, D-galactose, methyl-beta-D-galactoside, N-acetyl-D-galactosamine. Similar to plant lectins in its selective (carbohydrate-specific) hemagglutinating activity.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Pseudomonas aeruginosa is an opportunistic ESKAPE pathogen that produces two lectins, LecA and LecB, as part of its large arsenal of virulence factors. Both carbohydrate-binding proteins are central to the initial and later persistent infection processes, i. e. bacterial adhesion and biofilm formation. The biofilm matrix is a major resistance determinant and protects the bacteria against external threats such as the host immune system or antibiotic treatment. Therefore, the development of drugs against the P. aeruginosa biofilm is of particular interest to restore efficacy of antimicrobials. Carbohydrate-based inhibitors for LecA and LecB were previously shown to efficiently reduce biofilm formations. Here, we report a new approach for inhibiting LecA with synthetic molecules bridging the established carbohydrate-binding site and a central cavity located between two LecA protomers of the lectin tetramer. Inspired by in silico design, we synthesized various galactosidic LecA inhibitors with aromatic moieties targeting this central pocket. These compounds reached low micromolar affinities, validated in different biophysical assays. Finally, X-ray diffraction analysis revealed the interactions of this compound class with LecA. This new mode of action paves the way to a novel route towards inhibition of P. aeruginosa biofilms.
		+
		+	Targeting the Central Pocket of the Pseudomonas aeruginosa Lectin LecA.,Siebs E, Shanina E, Kuhaudomlarp S, da Silva Figueiredo Celestino Gomes P, Fortin C, Seeberger PH, Rognan D, Rademacher C, Imberty A, Titz A Chembiochem. 2022 Feb 4;23(3):e202100563. doi: 10.1002/cbic.202100563. Epub 2021 , Dec 2. PMID:34788491<ref>PMID:34788491</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7fio" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Galactose-binding lectin\|Galactose-binding lectin]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
		+	[[Category: Pseudomonas aeruginosa]]
	[[Category: Fortin C]]		[[Category: Fortin C]]
	[[Category: Imberty A]]		[[Category: Imberty A]]

OCA at 10:15, 16 February 2022

2022-02-16T10:15:40Z

←Older revision		Revision as of 10:15, 16 February 2022
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7fio is ~~ON HOLD until Paper Publication~~	+	==LecA from Pseudomonas aeruginosa in complex with a synthetic monovalent galactosidic inhibitor==
-		+	<StructureSection load='7fio' size='340' side='right'caption='[[7fio]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7FIO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7FIO 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=7fio FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7fio OCA], [https://pdbe.org/7fio PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7fio RCSB], [https://www.ebi.ac.uk/pdbsum/7fio PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7fio ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Fortin C]]
		+	[[Category: Imberty A]]
		+	[[Category: Kuhaudomlarp S]]
		+	[[Category: Rademacher C]]
		+	[[Category: Rognan D]]
		+	[[Category: Siebs E]]
		+	[[Category: Titz A]]
		+	[[Category: Da Silva Figueiredo Celestino Gomes P]]

OCA at 07:23, 8 September 2021

2021-09-08T07:23:17Z

←Older revision		Revision as of 07:23, 8 September 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors:		Authors:

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

2021-08-11T04:58:20Z

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

←Older revision

Revision as of 04:58, 11 August 2021

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

2021-08-11T04:58:20Z

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

New page

'''Unreleased structure'''

The entry 7fio is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]

7fio - Revision history

OCA at 17:16, 29 November 2023

OCA at 10:15, 16 February 2022

OCA at 07:23, 8 September 2021

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

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