View source for 7fio


==LecA from Pseudomonas aeruginosa in complex with a synthetic monovalent galactosidic inhibitor==
<StructureSection load='7fio' size='340' side='right'caption='[[7fio]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
== Structural highlights ==
<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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.5&#8491;</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>
== 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&reg;/PubMed&reg;, 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__
</StructureSection>
[[Category: Large Structures]]
[[Category: Pseudomonas aeruginosa]]
[[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]]