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| | ==Structure of Rivax: A Human Ricin Vaccine== | | ==Structure of Rivax: A Human Ricin Vaccine== |
| - | <StructureSection load='3srp' size='340' side='right' caption='[[3srp]], [[Resolution|resolution]] 2.14Å' scene=''> | + | <StructureSection load='3srp' size='340' side='right'caption='[[3srp]], [[Resolution|resolution]] 2.14Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3srp]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Castor_bean Castor bean]. The May 2013 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Ricin'' by David Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2013_5 10.2210/rcsb_pdb/mom_2013_5]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SRP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SRP FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3srp]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Ricinus_communis Ricinus communis]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3bjg 3bjg]. The May 2013 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Ricin'' by David Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2013_5 10.2210/rcsb_pdb/mom_2013_5]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SRP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SRP FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.14Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3bjg|3bjg]], [[3lc9|3lc9]], [[3mk9|3mk9]]</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='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=3srp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3srp OCA], [https://pdbe.org/3srp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3srp RCSB], [https://www.ebi.ac.uk/pdbsum/3srp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3srp 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=3srp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3srp OCA], [http://pdbe.org/3srp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3srp RCSB], [http://www.ebi.ac.uk/pdbsum/3srp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3srp 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 ==
| + | |
| - | RiVax is a recombinant protein that is currently under clinical development as part of a human vaccine to protect against ricin poisoning. RiVax includes ricin A-chain (RTA) residues 1-267 with two intentional amino-acid substitutions, V76M and Y80A, aimed at reducing toxicity. Here, the crystal structure of RiVax was solved to 2.1 A resolution and it was shown that it is superposable with that of the ricin toxin A-chain from Ricinus communis with a root-mean-square deviation of 0.6 A over 258 C(alpha) atoms. The RiVax structure is also compared with the recently determined structure of another potential ricin-vaccine immunogen, RTA 1-33/44-198 R48C/T77C. Finally, the locations and solvent-exposure of two toxin-neutralizing B-cell epitopes were examined and it was found that these epitopes are within or near regions predicted to be involved in catalysis. The results demonstrate the composition of the RiVax clinical material and will guide ongoing protein-engineering strategies to develop improved immunogens.
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| - | | + | |
| - | Structure of RiVax: a recombinant ricin vaccine.,Legler PM, Brey RN, Smallshaw JE, Vitetta ES, Millard CB Acta Crystallogr D Biol Crystallogr. 2011 Sep;67(Pt 9):826-30. doi:, 10.1107/S0907444911026771. Epub 2011 Aug 9. PMID:21904036<ref>PMID:21904036</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 3srp" style="background-color:#fffaf0;"></div>
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| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Ricin|Ricin]] | + | *[[Ricin 3D structures|Ricin 3D structures]] |
| - | == References ==
| + | |
| - | <references/>
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Castor bean]] | + | [[Category: Large Structures]] |
| | [[Category: RCSB PDB Molecule of the Month]] | | [[Category: RCSB PDB Molecule of the Month]] |
| | [[Category: Ricin]] | | [[Category: Ricin]] |
| - | [[Category: RRNA N-glycosylase]] | + | [[Category: Ricinus communis]] |
| - | [[Category: Legler, P M]] | + | [[Category: Legler PM]] |
| - | [[Category: Millard, C B]] | + | [[Category: Millard CB]] |
| - | [[Category: Hydrolase]]
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| - | [[Category: Immunogen]]
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| - | [[Category: Ribosome inactivating protein]]
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