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| | ==Crystal Structure of Pseudomonas aeruginosa Lectin LecA Complexed with GalA-WKY at 1.64 A Resolution== | | ==Crystal Structure of Pseudomonas aeruginosa Lectin LecA Complexed with GalA-WKY at 1.64 A Resolution== |
| - | <StructureSection load='4lkf' size='340' side='right' caption='[[4lkf]], [[Resolution|resolution]] 1.64Å' scene=''> | + | <StructureSection load='4lkf' size='340' side='right'caption='[[4lkf]], [[Resolution|resolution]] 1.64Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4lkf]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_aeruginosus"_(schroeter_1872)_trevisan_1885 "bacillus aeruginosus" (schroeter 1872) trevisan 1885]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LKF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4LKF FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4lkf]] 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=4LKF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LKF 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=GAL:BETA-D-GALACTOSE'>GAL</scene>, <scene name='pdbligand=PHB:P-HYDROXYBENZOIC+ACID'>PHB</scene></td></tr> | + | </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=GAL:BETA-D-GALACTOSE'>GAL</scene>, <scene name='pdbligand=PHB:P-HYDROXYBENZOIC+ACID'>PHB</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4lkd|4lkd]], [[4lke|4lke]]</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=4lkf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lkf OCA], [https://pdbe.org/4lkf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4lkf RCSB], [https://www.ebi.ac.uk/pdbsum/4lkf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4lkf ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">lecA pa1L PA2570 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=287 "Bacillus aeruginosus" (Schroeter 1872) Trevisan 1885])</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=4lkf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lkf OCA], [http://pdbe.org/4lkf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4lkf RCSB], [http://www.ebi.ac.uk/pdbsum/4lkf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4lkf ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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. | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Kadam, R U]] | + | [[Category: Large Structures]] |
| - | [[Category: Reymond, J L]] | + | [[Category: Pseudomonas aeruginosa]] |
| - | [[Category: Stocker, A]] | + | [[Category: Kadam RU]] |
| - | [[Category: Galactose]] | + | [[Category: Reymond J-L]] |
| - | [[Category: Lectin fold]] | + | [[Category: Stocker A]] |
| - | [[Category: Sugar binding protein-inhibitor complex]]
| + | |
| Structural highlights
Function
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.
Publication Abstract from PubMed
The galactopeptide dendrimer GalAG2 ((beta-Gal-OC6 H4 CO-Lys-Pro-Leu)4 (Lys-Phe-Lys-Ile)2 Lys-His-Ile-NH2 ) binds strongly to the Pseudomonas aeruginosa (PA) lectin LecA, and it inhibits PA biofilms, as well as disperses already established ones. By starting with the crystal structure of the terminal tripeptide moiety GalA-KPL in complex with LecA, a computational mutagenesis study was carried out on the galactotripeptide to optimize the peptide-lectin interactions. 25 mutants were experimentally evaluated by a hemagglutination inhibition assay, 17 by isothermal titration calorimetry, and 3 by X-ray crystallography. Two of these tripeptides, GalA-KPY (dissociation constant (KD )=2.7 muM) and GalA-KRL (KD =2.7 muM), are among the most potent monovalent LecA ligands reported to date. Dendrimers based on these tripeptide ligands showed improved PA biofilm inhibition and dispersal compared to those of GalAG2, particularly G2KPY ((beta-Gal-OC6 H4 CO-Lys-Pro-Tyr)4 (Lys-Phe-Lys-Ile)2 Lys-His-Ile-NH2 ). The possibility to retain and even improve the biofilm inhibition in several analogues of GalAG2 suggests that it should be possible to fine-tune this dendrimer towards therapeutic use by adjusting the pharmacokinetic parameters in addition to the biofilm inhibition through amino acid substitutions.
Structure-Based Optimization of the Terminal Tripeptide in Glycopeptide Dendrimer Inhibitors of Pseudomonas aeruginosa Biofilms Targeting LecA.,Kadam RU, Bergmann M, Garg D, Gabrieli G, Stocker A, Darbre T, Reymond JL Chemistry. 2013 Dec 9;19(50):17054-63. doi: 10.1002/chem.201302587. Epub 2013 Nov, 4. PMID:24307364[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kadam RU, Bergmann M, Garg D, Gabrieli G, Stocker A, Darbre T, Reymond JL. Structure-Based Optimization of the Terminal Tripeptide in Glycopeptide Dendrimer Inhibitors of Pseudomonas aeruginosa Biofilms Targeting LecA. Chemistry. 2013 Dec 9;19(50):17054-63. doi: 10.1002/chem.201302587. Epub 2013 Nov, 4. PMID:24307364 doi:http://dx.doi.org/10.1002/chem.201302587
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