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| | <StructureSection load='4q2v' size='340' side='right'caption='[[4q2v]], [[Resolution|resolution]] 2.20Å' scene=''> | | <StructureSection load='4q2v' size='340' side='right'caption='[[4q2v]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4q2v]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Castor_bean Castor bean]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Q2V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Q2V FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4q2v]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Ricinus_communis Ricinus communis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Q2V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Q2V FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0XE:5,6-DIHYDROXY-4-OXO-2-PHENYL-4H-CHROMEN-7-YL+BETA-D-GLUCOPYRANOSIDURONIC+ACID'>0XE</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]] 2.198Å</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=0XE:5,6-DIHYDROXY-4-OXO-2-PHENYL-4H-CHROMEN-7-YL+BETA-D-GLUCOPYRANOSIDURONIC+ACID'>0XE</scene></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=4q2v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4q2v OCA], [http://pdbe.org/4q2v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4q2v RCSB], [http://www.ebi.ac.uk/pdbsum/4q2v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4q2v 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=4q2v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4q2v OCA], [https://pdbe.org/4q2v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4q2v RCSB], [https://www.ebi.ac.uk/pdbsum/4q2v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4q2v 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== |
| - | *[[Ricin|Ricin]] | + | *[[Ricin 3D structures|Ricin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Castor bean]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: RRNA N-glycosylase]] | + | [[Category: Ricinus communis]] |
| - | [[Category: Chen, Y]] | + | [[Category: Chen Y]] |
| - | [[Category: Deng, X]] | + | [[Category: Deng X]] |
| - | [[Category: Dong, J]] | + | [[Category: Dong J]] |
| - | [[Category: Li, X]] | + | [[Category: Li X]] |
| - | [[Category: Baicalin complex]]
| + | |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
| + | |
| - | [[Category: Mixed alpha/beta structure]]
| + | |
| - | [[Category: Ribosome]]
| + | |
| - | [[Category: Ribosome-inactivating]]
| + | |
| 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
Toxic ribosome-inactivating proteins abolish cell viability by inhibiting protein synthesis. Ricin, a member of these lethal proteins, is a potential bioterrorism agent. Despite the grave challenge posed by these toxins to public health, post-exposure treatment for intoxication caused by these agents currently is unavailable. In this study, we report the identification of baicalin extracted from Chinese herbal medicine as a compound capable of inhibiting the activity of ricin. More importantly, post-exposure treatment with baicalin significantly increased the survival of mice poisoned by ricin. We determined the mechanism of action of baicalin by solving the crystal structure of its complex with the A chain of ricin (RTA) at 2.2 A resolution, which revealed that baicalin interacts with two RTA molecules at a novel binding site by hydrogen bond networks and electrostatic force interactions, suggesting its role as molecular glue of the RTA. Further biochemical and biophysical analyses validated the amino acids directly involved in binding the inhibitor, which is consistent with the hypothesis that baicalin exerts its inhibitory effects by inducing RTA to form oligomers in solution, a mechanism that is distinctly different from previously reported inhibitors. This work offers promising leads for the development of therapeutics against ricin and probably other ribosome-inactivating proteins.
Baicalin inhibits the lethality of ricin in mice by inducing protein oligomerization.,Dong J, Zhang Y, Chen Y, Niu X, Zhang Y, Li R, Yang C, Wang Q, Li X, Deng X J Biol Chem. 2015 May 15;290(20):12899-907. doi: 10.1074/jbc.M114.632828. Epub, 2015 Apr 5. PMID:25847243[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Dong J, Zhang Y, Chen Y, Niu X, Zhang Y, Li R, Yang C, Wang Q, Li X, Deng X. Baicalin inhibits the lethality of ricin in mice by inducing protein oligomerization. J Biol Chem. 2015 May 15;290(20):12899-907. doi: 10.1074/jbc.M114.632828. Epub, 2015 Apr 5. PMID:25847243 doi:http://dx.doi.org/10.1074/jbc.M114.632828
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