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| | ==Structure of the LecB lectin from Pseudomonas aeruginosa strain PA14 in complex with mannose-alpha1,3mannoside== | | ==Structure of the LecB lectin from Pseudomonas aeruginosa strain PA14 in complex with mannose-alpha1,3mannoside== |
| - | <StructureSection load='5a6y' size='340' side='right' caption='[[5a6y]], [[Resolution|resolution]] 1.40Å' scene=''> | + | <StructureSection load='5a6y' size='340' side='right'caption='[[5a6y]], [[Resolution|resolution]] 1.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5a6y]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Pseab Pseab]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5A6Y OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5A6Y FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5a6y]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa_UCBPP-PA14 Pseudomonas aeruginosa UCBPP-PA14]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5A6Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5A6Y FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</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]] 1.4Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5a6q|5a6q]], [[5a6x|5a6x]], [[5a6z|5a6z]], [[5a70|5a70]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=PRD_900112:3alpha-alpha-mannobiose'>PRD_900112</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5a6y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5a6y OCA], [http://pdbe.org/5a6y PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5a6y RCSB], [http://www.ebi.ac.uk/pdbsum/5a6y PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5a6y 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=5a6y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5a6y OCA], [https://pdbe.org/5a6y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5a6y RCSB], [https://www.ebi.ac.uk/pdbsum/5a6y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5a6y ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/A0A0H2ZE85_PSEAB A0A0H2ZE85_PSEAB] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Pseab]] | + | [[Category: Large Structures]] |
| - | [[Category: Haussler, s]] | + | [[Category: Pseudomonas aeruginosa UCBPP-PA14]] |
| - | [[Category: Imberty, A]] | + | [[Category: Haussler S]] |
| - | [[Category: Khaledi, a]] | + | [[Category: Imberty A]] |
| - | [[Category: Sommer, R]] | + | [[Category: Khaledi A]] |
| - | [[Category: Titz, A]] | + | [[Category: Sommer R]] |
| - | [[Category: Varrot, a]] | + | [[Category: Titz A]] |
| - | [[Category: Wagner, s]] | + | [[Category: Varrot A]] |
| - | [[Category: Hydrolase]]
| + | [[Category: Wagner S]] |
| - | [[Category: Lecb]]
| + | |
| - | [[Category: Lectin]]
| + | |
| Structural highlights
5a6y is a 4 chain structure with sequence from Pseudomonas aeruginosa UCBPP-PA14. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 1.4Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
A0A0H2ZE85_PSEAB
Publication Abstract from PubMed
P. aeruginosa causes a substantial number of nosocomial infections and is the leading cause of death of cystic fibrosis patients. This Gram-negative bacterium is highly resistant against antibiotics and further protects itself by forming a biofilm. Moreover, a high genomic variability among clinical isolates complicates therapy. Its lectin LecB is a virulence factor and necessary for adhesion and biofilm formation. We analyzed the sequence of LecB variants in a library of clinical isolates and demonstrate that it can serve as a marker for strain family classification. LecB from the highly virulent model strain PA14 presents 13% sequence divergence with LecB from the well characterized PAO1 strain. These differences might result in differing ligand binding specificities and ultimately in reduced efficacy of drugs directed towards LecB. Despite several amino acid variations at the carbohydrate binding site, glycan array analysis showed a comparable binding pattern for both variants. A common high affinity ligand could be identified and after its chemoenzymatic synthesis verified in a competitive binding assay: an N-glycan presenting two blood group O epitopes (H-type 2 antigen). Molecular modeling of the complex suggests a bivalent interaction of the ligand with the LecB tetramer by bridging two separate binding sites. This binding rationalizes the strong avidity (35 nM) of LecBPA14 to this human fucosylated N-glycan. Biochemical evaluation of a panel of glycan ligands revealed that LecBPA14 demonstrated higher glycan affinity compared to LecBPAO1 including the extraordinarily potent affinity of 70 nM towards the monovalent human antigen Lewis(a). The structural basis of this unusual high affinity ligand binding for lectins was rationalized by solving the protein crystal structures of LecBPA14 with several glycans.
The virulence factor LecB varies in clinical isolates: consequences for ligand binding and drug discovery.,Sommer R, Wagner S, Varrot A, Nycholat CM, Khaledi A, Haussler S, Paulson JC, Imberty A, Titz A Chem Sci. 2016 Aug 1;7(8):4990-5001. doi: 10.1039/c6sc00696e. Epub 2016 May 11. PMID:30155149[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Sommer R, Wagner S, Varrot A, Nycholat CM, Khaledi A, Haussler S, Paulson JC, Imberty A, Titz A. The virulence factor LecB varies in clinical isolates: consequences for ligand binding and drug discovery. Chem Sci. 2016 Aug 1;7(8):4990-5001. doi: 10.1039/c6sc00696e. Epub 2016 May 11. PMID:30155149 doi:http://dx.doi.org/10.1039/c6sc00696e
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