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| | <StructureSection load='6ikm' size='340' side='right'caption='[[6ikm]], [[Resolution|resolution]] 3.40Å' scene=''> | | <StructureSection load='6ikm' size='340' side='right'caption='[[6ikm]], [[Resolution|resolution]] 3.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6ikm]] is a 36 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=6IKM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6IKM FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6ikm]] is a 36 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6IKM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6IKM FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=SPD:SPERMIDINE'>SPD</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]] 3.398Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6ikr|6ikr]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=SPD:SPERMIDINE'>SPD</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=6ikm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ikm OCA], [http://pdbe.org/6ikm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ikm RCSB], [http://www.ebi.ac.uk/pdbsum/6ikm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ikm 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=6ikm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ikm OCA], [https://pdbe.org/6ikm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ikm RCSB], [https://www.ebi.ac.uk/pdbsum/6ikm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ikm ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/SPUE_PSEAE SPUE_PSEAE] Spermidine-binding protein probably required for its uptake into cells. Binds spermidine with high affinity (KD=14.3 nM). Does not bind putrescine, cadaverine or spermine. Spermidine binding induces large inter-domain conformational changes. Implicated in induction of type 3 secretion systems (T3SS), which play a role in virulence.<ref>PMID:22300763</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6ikm" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6ikm" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Antibody 3D structures|Antibody 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Sun, X]] | + | [[Category: Pseudomonas aeruginosa]] |
| - | [[Category: Wu, D]] | + | [[Category: Sun X]] |
| - | [[Category: Antibody]] | + | [[Category: Wu D]] |
| - | [[Category: Antimicrobial protein]]
| + | |
| - | [[Category: Atp binding cassette]]
| + | |
| - | [[Category: Spue]]
| + | |
| - | [[Category: Type three secretion system]]
| + | |
| Structural highlights
Function
SPUE_PSEAE Spermidine-binding protein probably required for its uptake into cells. Binds spermidine with high affinity (KD=14.3 nM). Does not bind putrescine, cadaverine or spermine. Spermidine binding induces large inter-domain conformational changes. Implicated in induction of type 3 secretion systems (T3SS), which play a role in virulence.[1]
Publication Abstract from PubMed
Multidrug-resistant gram-negative bacteria infection is particularly severe within the designated ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species), which underscores the urgent need to explore alternative therapeutic strategies. The type III secretion system (T3SS) is considered to be a key virulence factor in many gram-negative bacteria, and T3SS is in turn regulated by SpuE in P. aeruginosa, which is a spermidine binding protein from an ATP-binding cassette transporter family and highly conserved within ESKAPE pathogens. Here, we identified a potent anti-SpuE antagonistic antibody that allosterically inhibits the expression of T3SS and attenuates virulence of P. aeruginosa. X-ray crystallography and molecular dynamics simulations revealed that binding of antibody to SpuE induces a change in the dynamics of SpuE, which in turn may reduce spermidine uptake by P. aeruginosa. The antibody could serve as a template for developing novel biologics to target a broad spectrum of gram-negative bacteria.
A Potent Anti-SpuE Antibody Allosterically Inhibits Type III Secretion System and Attenuates Virulence of Pseudomonas Aeruginosa.,Zhang Y, Sun X, Qian Y, Yi H, Song K, Zhu H, Zonta F, Chen W, Ji Q, Miersch S, Sidhu SS, Wu D J Mol Biol. 2019 Dec 6;431(24):4882-4896. doi: 10.1016/j.jmb.2019.10.026. Epub, 2019 Nov 2. PMID:31682834[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Wu D, Lim SC, Dong Y, Wu J, Tao F, Zhou L, Zhang LH, Song H. Structural Basis of Substrate Binding Specificity Revealed by the Crystal Structures of Polyamine Receptors SpuD and SpuE from Pseudomonas aeruginosa. J Mol Biol. 2012 Mar 9;416(5):697-712. Epub 2012 Jan 28. PMID:22300763 doi:10.1016/j.jmb.2012.01.010
- ↑ Zhang Y, Sun X, Qian Y, Yi H, Song K, Zhu H, Zonta F, Chen W, Ji Q, Miersch S, Sidhu SS, Wu D. A Potent Anti-SpuE Antibody Allosterically Inhibits Type III Secretion System and Attenuates Virulence of Pseudomonas Aeruginosa. J Mol Biol. 2019 Dec 6;431(24):4882-4896. doi: 10.1016/j.jmb.2019.10.026. Epub, 2019 Nov 2. PMID:31682834 doi:http://dx.doi.org/10.1016/j.jmb.2019.10.026
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