3ej5 | pdb_00003ej5

complex of Ricin A chain and pyrimidine-based inhibitor

spinqualitylabelsall models 3ej5, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3ej5 is a 1 chain structure with sequence from Ricinus communis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.5Å Ligands: EJ5 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Ricin is a potent heterodimeric cytotoxin; the B chain binds eucaryotic cell surfaces aiding uptake and the A chain, RTA, reaches the cytoplasm where it enzymatically depurinates a key ribosomal adenine, inhibiting protein synthesis. Ricin is known to be an agent in bioterrorist repertoires and there is great interest in finding, or creating, efficacious inhibitors of the toxin as potential antidotes. We have previously identified two families of bicyclic RTA inhibitors, pterins and purines. Both classes have poor solubility which impairs inhibitor development. Here we report the use of 2-amino-4,6-dihydroxy-pyrimidines as RTA inhibitors. Unlike previously observed single ring inhibitor platforms, these displace Tyr 80 and bind deep in the RTA specificity pocket. These compounds are at least 10 times more soluble than pterin-based inhibitors and appear to be useful new class of ricin inhibitors. The X-ray structure of ricin A chain with a novel inhibitor.,Bai Y, Monzingo AF, Robertus JD Arch Biochem Biophys. 2009 Mar 1;483(1):23-8. Epub 2008 Dec 30. PMID:19138659 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ricin 3D structures

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