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New page: '''Unreleased structure''' The entry 4odt is ON HOLD Authors: Haji-Ghassemi, O., Evans, S.V. Description: Fab Structure of lipid A-specific antibody S1-15 in complex with lipid A carbo...
 
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'''Unreleased structure'''


The entry 4odt is ON HOLD
==Fab Structure of lipid A-specific antibody S1-15 in complex with lipid A carbohydrate backbone==
<StructureSection load='4odt' size='340' side='right'caption='[[4odt]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4odt]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ODT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ODT 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]] 1.95&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GP1:GLUCOSAMINE+1-PHOSPHATE'>GP1</scene>, <scene name='pdbligand=PG0:2-(2-METHOXYETHOXY)ETHANOL'>PG0</scene>, <scene name='pdbligand=Z9M:2-AMINO-2-DEOXY-4-O-PHOSPHONO-BETA-D-GLUCOPYRANOSE'>Z9M</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=4odt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4odt OCA], [https://pdbe.org/4odt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4odt RCSB], [https://www.ebi.ac.uk/pdbsum/4odt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4odt ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Septic shock is a leading cause of death, and, results from an inflammatory cascade triggered by the presence of microbial products in the blood. Certain LPS from Gram-negative bacteria are very potent inducers and responsible for a high percentage of septic shock cases. Despite decades of research, mAbs specific for lipid A (the endotoxic principle of LPS) have not been successfully developed into a clinical treatment for sepsis. To understand the molecular basis for the observed inability to translate in vitro specificity for lipid A into clinical potential, the structures of antigen binding fragments of mAbs S1-15 and A6 have been determined unliganded and in complex with lipid A carbohydrate backbone. The two antibodies have separate germ-line origins that generate two markedly different combining-site pockets that are complementary both in shape and charge to the antigen. MAb A6 binds lipid A through both variable light and heavy chain residues, while S1-15 utilizes exclusively the variable heavy chain. Both antibodies bind lipid A such that the GlcN-O6 attachment point for the core oligosaccharide is buried in the combining site, which explains the lack of LPS recognition. Longstanding reports of polyspecificity of anti-lipid A antibodies towards single stranded DNA combined with observed homology of S1-15 and A6 and the reports of several single stranded DNA-specific mAbs prompted the determination of the structure of S1-15 in complex with ssDNA fragments, which may provide clues into the genesis of autoimmune diseases such as systemic lupus erythematosus, thyroiditis, and rheumatic autoimmune diseases.


Authors: Haji-Ghassemi, O., Evans, S.V.
Structural Basis for Antibody Recognition of Lipid A: Insights to Polyspecificity Toward Single Stranded DNA.,Haji-Ghassemi O, Muller-Loennies S, Rodriguez T, Brade L, Kosma P, Brade H, Evans SV J Biol Chem. 2015 Jun 17. pii: jbc.M115.657874. PMID:26085093<ref>PMID:26085093</ref>


Description: Fab Structure of lipid A-specific antibody S1-15 in complex with lipid A carbohydrate backbone
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4odt" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Evans SV]]
[[Category: Haji-Ghassemi O]]
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