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| <StructureSection load='4lhq' size='340' side='right'caption='[[4lhq]], [[Resolution|resolution]] 2.30Å' scene=''> | | <StructureSection load='4lhq' size='340' side='right'caption='[[4lhq]], [[Resolution|resolution]] 2.30Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[4lhq]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Alpaca Alpaca] and [http://en.wikipedia.org/wiki/Castor_bean Castor bean]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LHQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4LHQ FirstGlance]. <br> | | <table><tr><td colspan='2'>[[4lhq]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Ricinus_communis Ricinus communis] and [https://en.wikipedia.org/wiki/Vicugna_pacos Vicugna pacos]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LHQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LHQ FirstGlance]. <br> |
| </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4lgp|4lgp]], [[4lgr|4lgr]], [[4lgs|4lgs]], [[4lhj|4lhj]]</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]] 2.3Å</td></tr> |
| <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/rRNA_N-glycosylase rRNA N-glycosylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.2.22 3.2.2.22] </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=4lhq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lhq OCA], [https://pdbe.org/4lhq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4lhq RCSB], [https://www.ebi.ac.uk/pdbsum/4lhq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4lhq ProSAT]</span></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=4lhq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lhq OCA], [http://pdbe.org/4lhq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4lhq RCSB], [http://www.ebi.ac.uk/pdbsum/4lhq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4lhq ProSAT]</span></td></tr> | |
| </table> | | </table> |
| == Function == | | == Function == |
| [[http://www.uniprot.org/uniprot/RICI_RICCO RICI_RICCO]] Ricin is highly toxic to animal cells and to a lesser extent to plant cells. The A chain acts as a glycosidase that removes a specific adenine residue from an exposed loop of the 28S rRNA (A4324 in mammals), leading to rRNA breakage. As this loop is involved in elongation factor binding, modified ribosomes are catalytically inactive and unable to support protein synthesis. The A chain can inactivate a few thousand ribosomes per minute, faster than the cell can make new ones. Therefore a single A chain molecule can kill an animal cell. The B chain binds to beta-D-galactopyranoside moieties on cell surface glycoproteins and glycolipids and facilitates the entry into the cell of the A chain; B chains are also responsible for cell agglutination (Lectin activity). | | [https://www.uniprot.org/uniprot/RICI_RICCO RICI_RICCO] Ricin is highly toxic to animal cells and to a lesser extent to plant cells. The A chain acts as a glycosidase that removes a specific adenine residue from an exposed loop of the 28S rRNA (A4324 in mammals), leading to rRNA breakage. As this loop is involved in elongation factor binding, modified ribosomes are catalytically inactive and unable to support protein synthesis. The A chain can inactivate a few thousand ribosomes per minute, faster than the cell can make new ones. Therefore a single A chain molecule can kill an animal cell. The B chain binds to beta-D-galactopyranoside moieties on cell surface glycoproteins and glycolipids and facilitates the entry into the cell of the A chain; B chains are also responsible for cell agglutination (Lectin activity). |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| Ricin is a select agent toxin and a member of the RNA N-glycosidase family of medically important plant and bacterial ribosome-inactivating proteins. In this study, we determined X-ray crystal structures of the enzymatic subunit of ricin (RTA) in complex with the antigen binding domains (VHH) of five unique single-chain monoclonal antibodies that differ in their respective toxin-neutralizing activities. None of the VHHs made direct contact with residues involved in RTA's RNA N-glycosidase activity or induced notable allosteric changes in the toxin's subunit. Rather, the five VHHs had overlapping structural epitopes on the surface of the toxin and differed in the degree to which they made contact with prominent structural elements in two folding domains of the RTA. In general, RTA interactions were influenced most by the VHH CDR3 (CDR, complementarity-determining region) elements, with the most potent neutralizing antibody having the shortest and most conformationally constrained CDR3. These structures provide unique insights into the mechanisms underlying toxin neutralization and provide critically important information required for the rational design of ricin toxin subunit vaccines.
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| Crystal Structures of Ricin Toxin's Enzymatic Subunit (RTA) in Complex with Neutralizing and Non-Neutralizing Single-Chain Antibodies.,Rudolph MJ, Vance DJ, Cheung J, Franklin MC, Burshteyn F, Cassidy MS, Gary EN, Herrera C, Shoemaker CB, Mantis NJ J Mol Biol. 2014 Jun 4. pii: S0022-2836(14)00276-9. doi:, 10.1016/j.jmb.2014.05.026. PMID:24907552<ref>PMID:24907552</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 4lhq" style="background-color:#fffaf0;"></div>
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| ==See Also== | | ==See Also== |
| *[[Ricin|Ricin]] | | *[[Ricin 3D structures|Ricin 3D structures]] |
| == References ==
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| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Alpaca]]
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| [[Category: Castor bean]]
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| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: RRNA N-glycosylase]] | | [[Category: Ricinus communis]] |
| [[Category: Burshteyn, F]] | | [[Category: Vicugna pacos]] |
| [[Category: Cassidy, M]] | | [[Category: Burshteyn F]] |
| [[Category: Cheung, J]] | | [[Category: Cassidy M]] |
| [[Category: Franklin, M]] | | [[Category: Cheung J]] |
| [[Category: Gary, E]] | | [[Category: Franklin M]] |
| [[Category: Mantis, N]] | | [[Category: Gary E]] |
| [[Category: Rudolph, M J]] | | [[Category: Mantis N]] |
| [[Category: Hydrolase-immune system complex]]
| | [[Category: Rudolph MJ]] |
| [[Category: Ribosome inhibiting protein]]
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