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| | <StructureSection load='6obg' size='340' side='right'caption='[[6obg]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='6obg' size='340' side='right'caption='[[6obg]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6obg]] 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=6OBG OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6OBG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6obg]] 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=6OBG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OBG FirstGlance]. <br> |
| - | </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=ZN:ZINC+ION'>ZN</scene></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]] 1.996Å</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='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=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6obg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6obg OCA], [http://pdbe.org/6obg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6obg RCSB], [http://www.ebi.ac.uk/pdbsum/6obg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6obg ProSAT]</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=6obg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6obg OCA], [https://pdbe.org/6obg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6obg RCSB], [https://www.ebi.ac.uk/pdbsum/6obg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6obg 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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| | *[[Antibody 3D structures|Antibody 3D structures]] | | *[[Antibody 3D structures|Antibody 3D structures]] |
| | + | *[[Ricin 3D structures|Ricin 3D structures]] |
| | *[[3D structures of non-human antibody|3D structures of non-human antibody]] | | *[[3D structures of non-human antibody|3D structures of non-human antibody]] |
| | == References == | | == References == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Alpaca]] | |
| - | [[Category: Castor bean]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: RRNA N-glycosylase]] | + | [[Category: Ricinus communis]] |
| - | [[Category: Rudolph, M J]] | + | [[Category: Vicugna pacos]] |
| - | [[Category: Toxin]] | + | [[Category: Rudolph MJ]] |
| Structural highlights
Function
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).
Publication Abstract from PubMed
The extreme potency of the plant toxin, ricin, is due to its enzymatic subunit, RTA, which inactivates mammalian ribosomes with near-perfect efficiency. Here we characterized, at the functional and structural levels, seven alpaca single-domain antibodies (VHHs) previously reported to recognize epitopes in proximity to RTA's active site. Three of the VHHs, V2A11, V8E6, and V2G10, were potent inhibitors of RTA in vitro and protected Vero cells from ricin when expressed as intracellular antibodies ("intrabodies"). Crystal structure analysis revealed that the complementarity-determining region 3 (CDR3) elements of V2A11 and V8E6 penetrate RTA's active site and interact with key catalytic residues. V2G10, by contrast, sits atop the enzymatic pocket and occludes substrate accessibility. The other four VHHs also penetrated/occluded RTA's active site, but lacked sufficient binding affinities to outcompete RTA-ribosome interactions. Intracellular delivery of high-affinity, single-domain antibodies may offer a new avenue in the development of countermeasures against ricin toxin.toxin, antibody, structure, intracellular.
Intracellular Neutralization of Ricin Toxin by Single-domain Antibodies Targeting the Active Site.,Rudolph MJ, Czajka TF, Davis SA, Thi Nguyen CM, Li XP, Tumer NE, Vance DJ, Mantis NJ J Mol Biol. 2020 Feb 14;432(4):1109-1125. doi: 10.1016/j.jmb.2020.01.006. Epub, 2020 Jan 10. PMID:31931008[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Rudolph MJ, Czajka TF, Davis SA, Thi Nguyen CM, Li XP, Tumer NE, Vance DJ, Mantis NJ. Intracellular Neutralization of Ricin Toxin by Single-domain Antibodies Targeting the Active Site. J Mol Biol. 2020 Feb 14;432(4):1109-1125. doi: 10.1016/j.jmb.2020.01.006. Epub, 2020 Jan 10. PMID:31931008 doi:http://dx.doi.org/10.1016/j.jmb.2020.01.006
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