6z6c
From Proteopedia
(Difference between revisions)
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==Crystal structurel of FleA lectin in complex with a monovalent inhibitor== | ==Crystal structurel of FleA lectin in complex with a monovalent inhibitor== | ||
| - | <StructureSection load='6z6c' size='340' side='right'caption='[[6z6c]]' scene=''> | + | <StructureSection load='6z6c' size='340' side='right'caption='[[6z6c]], [[Resolution|resolution]] 1.40Å' 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=6Z6C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6Z6C FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6z6c]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspfu Aspfu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Z6C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6Z6C 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=6z6c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6z6c OCA], [https://pdbe.org/6z6c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6z6c RCSB], [https://www.ebi.ac.uk/pdbsum/6z6c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6z6c 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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=Q9Q:4-((1-(2-(2-(2-(2-hydroxyethoxy)ethoxy)ethoxy)ethyl)-1H-1,2,3-triazol-4-yl)methoxy)benzyl-a-L-thiofucoside'>Q9Q</scene></td></tr> |
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">fleA, AFUA_5G14740 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=330879 ASPFU])</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=6z6c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6z6c OCA], [https://pdbe.org/6z6c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6z6c RCSB], [https://www.ebi.ac.uk/pdbsum/6z6c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6z6c ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [[https://www.uniprot.org/uniprot/LECF_ASPFU LECF_ASPFU]] Multispecific lectin that is able to recognize L-fucose in all possible linkages (PubMed:23695231, PubMed:27058347, PubMed:24340081, PubMed:25760594). These could be found not only in decomposed plant matter in soil, which is the natural environment for A.fumigatus, but also in various epitopes on human tissues (PubMed:25760594). Mediates binding of A.fumigatus conidia to airway mucinin a fucose dependent manner (PubMed:27058347). Stimulates IL-8 production by human bronchial cells in a dose-dependent manner, contributing to the inflammatory response observed upon the exposure of a patient to A.fumigatus, and thus might be an important virulence factor involved in an early stage of A.fumigatus infection (PubMed:24340081).<ref>PMID:23695231</ref> <ref>PMID:24340081</ref> <ref>PMID:25760594</ref> <ref>PMID:27058347</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Aspergillus fumigatus is a pathogenic fungus infecting the respiratory system and responsible for a variety of life-threatening lung diseases. A fucose-binding lectin named FleA which has a controversial role in A. fumigatus pathogenesis was recently identified. New chemical probes with high affinity and enzymatic stability are needed to explore the role of FleA in the infection process. In this study, we developed potent FleA antagonists based on optimized and non-hydrolysable thiofucoside ligands. We first synthesized a set of monovalent sugars showing micromolar affinity for FleA by isothermal titration calorimetry. The most potent derivative was co-crystallized with FleA to gain insights into the binding mode in operation. Its chemical multimerization on a cyclodextrin scaffold led to an hexavalent compound with a significantly enhanced binding affinity (Kd = 223 +/- 21 nM) thanks to a chelate binding mode. The compound could probe the role of bronchial epithelial cells in a FleA-mediated response to tissue invasion. | ||
| + | |||
| + | Hexavalent thiofucosides to probe the role of the Aspergillus fumigatus lectin FleA in fungal pathogenicity.,Dussouy C, Lalys PA, Cabanettes A, Lehot V, Deniaud D, Gillon E, Balloy V, Varrot A, Gouin SG Org Biomol Chem. 2021 Apr 14;19(14):3234-3240. doi: 10.1039/d1ob00152c. Epub 2021, Mar 24. PMID:33885578<ref>PMID:33885578</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6z6c" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Aspfu]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Varrot A]] | + | [[Category: Varrot, A]] |
| + | [[Category: Antiadhesive]] | ||
| + | [[Category: Fucose binding]] | ||
| + | [[Category: Lectin]] | ||
| + | [[Category: Sugar binding protein]] | ||
Revision as of 09:01, 5 May 2021
Crystal structurel of FleA lectin in complex with a monovalent inhibitor
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