4b8y: Difference between revisions
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==Ferrichrome-bound FhuD2== | |||
<StructureSection load='4b8y' size='340' side='right'caption='[[4b8y]], [[Resolution|resolution]] 1.90Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4b8y]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus_subsp._aureus_NCTC_8325 Staphylococcus aureus subsp. aureus NCTC 8325] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4B8Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4B8Y 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]] 1.9Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AHO:N-ACETYL-N-HYDROXY-L-ORNITHINE'>AHO</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</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=4b8y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4b8y OCA], [https://pdbe.org/4b8y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4b8y RCSB], [https://www.ebi.ac.uk/pdbsum/4b8y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4b8y ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q2FVW9_STAA8 Q2FVW9_STAA8] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Staphylococcus aureus is a human pathogen causing globally significant morbidity and mortality. The development of antibiotic resistance in S. aureus highlights the need for a preventive vaccine. Here we explore the structure and function of FhuD2, a staphylococcal surface lipoprotein mediating iron-uptake during invasive infection, recently described as a promising vaccine candidate. Differential scanning fluorimetry and calorimetry studies revealed that FhuD2 is stabilized by hydroxamate siderophores. The FhuD2-ferrichrome interaction was of nanomolar affinity in surface plasmon resonance experiments and fully Fe3+-dependent. We determined the x-ray crystallographic structure of ligand-bound FhuD2 at 1.9A resolution, revealing the bilobate fold of class III solute-binding proteins (SBPs). The ligand, ferrichrome, occupies a cleft between the FhuD2 N- and C-terminal lobes. Many FhuD2-siderophore interactions enable the specific recognition of ferrichrome. Biochemical data suggest that FhuD2 does not undergo significant conformational changes upon siderophore binding, supporting the hypothesis that the ligand-bound complex is essential for receptor engagement and uptake. Finally, immunizations with FhuD2 alone or FhuD2 formulated with hydroxamate siderophores were equally protective in a murine staphylococcal infection model, confirming the suitability and efficacy of apo-FhuD2 as a protective antigen, and suggesting that other Class III SBPs might also be exploited as vaccine candidates. | |||
Structural and functional characterization of the Staphylococcus aureus virulence factor and vaccine candidate FhuD2.,Mariotti P, Malito E, Biancucci M, Lo Surdo P, Mishra RP, Nardi-Dei V, Savino S, Nissum M, Spraggon G, Grandi G, Bagnoli F, Bottomley MJ Biochem J. 2012 Oct 31. PMID:23113737<ref>PMID:23113737</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4b8y" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Staphylococcus aureus subsp. aureus NCTC 8325]] | |||
[[Category: Synthetic construct]] | |||
[[Category: Bottomley MJ]] | |||
[[Category: Malito E]] | |||
[[Category: Spraggon G]] | |||
