View source for 5boz


==Ricin A chain bound to camelid nanobody (VHH9)(E1)==
<StructureSection load='5boz' size='340' side='right'caption='[[5boz]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5boz]] is a 12 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=5BOZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5BOZ 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]] 3.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <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=5boz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5boz OCA], [https://pdbe.org/5boz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5boz RCSB], [https://www.ebi.ac.uk/pdbsum/5boz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5boz ProSAT]</span></td></tr>
</table>
== Function ==
[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;">
== Publication Abstract from PubMed ==
Ricin toxin is a heterodimer consisting of RTA, a ribosome-inactivating protein, and RTB, a lectin that facilitates receptor-mediated uptake into mammalian cells. In previous studies, we demonstrated that toxin-neutralizing antibodies target four spatially distinct hotspots on RTA, which we refer to as epitope Clusters I-IV. In this report we identified and characterized three single domain camelid antibodies (VHH) against Cluster II. One of these VHHs, V5E1, ranks as one of the most potent ricin-neutralizing antibodies described to date. We solved the X-ray crystal structures of each of the three VHHs (E1, V1C7 and V5E1) in complex with RTA. V5E1 buries a total of 1,133 A2 of surface area on RTA and makes primary contacts with alpha-helix A (residues 18-32), alpha-helix F (182-194), as well as the F-G loop. V5E1, by virtue of complementary determining region 3 (CDR3), may also engage with RTB and potentially interfere with the high affinity galactose-recognition element that plays a critical role in toxin attachment to cell surfaces and intracellular trafficking. The two other VHHs, E1 and V1C7, bind epitopes adjacent to V5E1 but display only weak toxin-neutralizing activity, thereby providing the first structural insights into specific residues within Cluster II that may be critical contact points for toxin inactivation.

Structural analysis of single domain antibodies bound to a second neutralizing hot spot on ricin toxin's enzymatic subunit.,Rudolph MJ, Vance DJ, Cassidy MS, Rong Y, Mantis NJ J Biol Chem. 2016 Nov 30. pii: jbc.M116.758102. PMID:27903650<ref>PMID:27903650</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5boz" style="background-color:#fffaf0;"></div>

==See Also==
*[[Antibody 3D structures|Antibody 3D structures]]
*[[3D structures of non-human antibody|3D structures of non-human antibody]]
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Ricinus communis]]
[[Category: Vicugna pacos]]
[[Category: Mantis N]]
[[Category: Rudolph MJ]]