4u6v: Difference between revisions
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==Mechanisms of Neutralization of a Human Anti-Alpha Toxin Antibody== | |||
<StructureSection load='4u6v' size='340' side='right'caption='[[4u6v]], [[Resolution|resolution]] 2.56Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4u6v]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Staphylococcus_aureus_subsp._aureus_TCH60 Staphylococcus aureus subsp. aureus TCH60]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4U6V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4U6V 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]] 2.56Å</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></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=4u6v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u6v OCA], [https://pdbe.org/4u6v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4u6v RCSB], [https://www.ebi.ac.uk/pdbsum/4u6v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4u6v ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/HLA_STAA8 HLA_STAA8] Alpha-toxin binds to the membrane of eukaryotic cells resulting in the release of low-molecular weight molecules and leading to an eventual osmotic lysis. Heptamer oligomerization and pore formation is required for lytic activity (By similarity). | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
MEDI4893 is a neutralizing human monoclonal antibody that targets alpha toxin (AT), and is currently undergoing evaluation in the field of Staphylococcus aureus-mediated diseases. We have solved the crystal structure of MEDI4893 Fab bound to monomeric AT at a resolution of 2.56 A, and further characterized its epitope using various engineered AT variants. We have found that MEDI4893 recognizes a novel epitope in AT so-called rim domain, and exerts its neutralizing effect through a dual mechanism. More particularly, MEDI4893 not only sterically blocks binding of AT to its cell receptor, but also prevents it from adopting a lytic heptameric trans-membrane conformation. | |||
Mechanisms of Neutralization of a Human Anti-Alpha Toxin Antibody.,Oganesyan V, Peng L, Damschroder MM, Cheng L, Sadowska A, Tkaczyk C, Sellman BR, Wu H, Dall'Acqua WF J Biol Chem. 2014 Sep 10. pii: jbc.M114.601328. PMID:25210036<ref>PMID:25210036</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4u6v" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Hemolysin 3D structures|Hemolysin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Staphylococcus aureus subsp. aureus TCH60]] | |||
[[Category: Cheng L]] | |||
[[Category: Dall'Acqua WF]] | |||
[[Category: Damschroder MM]] | |||
[[Category: Oganesyan VY]] | |||
[[Category: Peng L]] | |||
[[Category: Sadowska A]] | |||
[[Category: Sellman B]] | |||
[[Category: Tkaczyk C]] | |||
[[Category: Wu H]] | |||