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| | <StructureSection load='4huo' size='340' side='right'caption='[[4huo]], [[Resolution|resolution]] 1.52Å' scene=''> | | <StructureSection load='4huo' size='340' side='right'caption='[[4huo]], [[Resolution|resolution]] 1.52Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4huo]] 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=4HUO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HUO FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4huo]] 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=4HUO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HUO FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=RS8:N-[(2-AMINO-4-OXO-1,4-DIHYDROPTERIDIN-7-YL)CARBONYL]GLYCYL-L-PHENYLALANINE'>RS8</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=RS8:N-[(2-AMINO-4-OXO-1,4-DIHYDROPTERIDIN-7-YL)CARBONYL]GLYCYL-L-PHENYLALANINE'>RS8</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1rtc|1rtc]], [[1ift|1ift]], [[1br6|1br6]], [[3px8|3px8]], [[3px9|3px9]], [[4esi|4esi]], [[4hup|4hup]], [[4hv3|4hv3]], [[4hv7|4hv7]]</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=4huo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4huo OCA], [https://pdbe.org/4huo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4huo RCSB], [https://www.ebi.ac.uk/pdbsum/4huo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4huo ProSAT]</span></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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4huo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4huo OCA], [http://pdbe.org/4huo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4huo RCSB], [http://www.ebi.ac.uk/pdbsum/4huo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4huo 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: Anslyn, E V]] | + | [[Category: Anslyn EV]] |
| - | [[Category: Jasheway, K R]] | + | [[Category: Jasheway KR]] |
| - | [[Category: Manzano, L A]] | + | [[Category: Manzano LA]] |
| - | [[Category: Monzingo, A F]] | + | [[Category: Monzingo AF]] |
| - | [[Category: Pruet, J M]] | + | [[Category: Pruet JM]] |
| - | [[Category: Robertus, J D]] | + | [[Category: Robertus JD]] |
| - | [[Category: Saito, R]] | + | [[Category: Saito R]] |
| - | [[Category: Wiget, P A]] | + | [[Category: Wiget PA]] |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
| + | |
| - | [[Category: N-glycosidase]]
| + | |
| - | [[Category: Protein-ligand complex]]
| + | |
| - | [[Category: Pterin]]
| + | |
| - | [[Category: Ribosome-inactivating protein]]
| + | |
| - | [[Category: Ricin]]
| + | |
| - | [[Category: Toxin]]
| + | |
| 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
Several 7-peptide-substituted pterins were synthesized and tested as competitive active-site inhibitors of ricin toxin A (RTA). Focus began on dipeptide conjugates, and these results further guided the construction of several tripeptide conjugates. The binding of these compounds to RTA was studied via a luminescence-based kinetic assay, as well as through X-ray crystallography. Despite the relatively polar, solvent exposed active site, several hydrophobic interactions, most commonly pi-interactions not predicted by modeling programs, were identified in all of the best-performing inhibitors. Nearly all of these compounds provide IC(50) values in the low micromolar range.
Peptide-Conjugated Pterins as Inhibitors of Ricin Toxin A.,Saito R, Pruet JM, Manzano LA, Jasheway K, Monzingo AF, Wiget PA, Kamat I, Anslyn EV, Robertus JD J Med Chem. 2012 Dec 19. PMID:23214944[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Saito R, Pruet JM, Manzano LA, Jasheway K, Monzingo AF, Wiget PA, Kamat I, Anslyn EV, Robertus JD. Peptide-Conjugated Pterins as Inhibitors of Ricin Toxin A. J Med Chem. 2012 Dec 19. PMID:23214944 doi:http://dx.doi.org/10.1021/jm3016393
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