1qnu | pdb_00001qnu

Shiga-Like Toxin I B Subunit Complexed with the Bridged-Starfish Inhibitor

spinqualitylabelsall models 1qnu, resolution 2.23Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1qnu is a 5 chain structure with sequence from Escherichia coli O157:H7. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.23Å Ligands: EMB, GAL, GLC, MEC Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function V5URS0_9CAUD The B subunit is responsible for the binding of the holotoxin to specific receptors on the target cell surface, such as globotriaosylceramide (Gb3) in human intestinal microvilli.[ARBA:ARBA00003218] 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 The diseases caused by Shiga and cholera toxins account for the loss of millions of lives each year. Both belong to the clinically significant subset of bacterial AB5 toxins consisting of an enzymatically active A subunit that gains entry to susceptible mammalian cells after oligosaccharide recognition by the B5 homopentamer. Therapies might target the obligatory oligosaccharide-toxin recognition event, but the low intrinsic affinity of carbohydrate-protein interactions hampers the development of low-molecular-weight inhibitors. The toxins circumvent low affinity by binding simultaneously to five or more cell-surface carbohydrates. Here we demonstrate the use of the crystal structure of the B5 subunit of Escherichia coli O157:H7 Shiga-like toxin I (SLT-I) in complex with an analogue of its carbohydrate receptor to design an oligovalent, water-soluble carbohydrate ligand (named STARFISH), with subnanomolar inhibitory activity. The in vitro inhibitory activity is 1-10-million-fold higher than that of univalent ligands and is by far the highest molar activity of any inhibitor yet reported for Shiga-like toxins I and II. Crystallography of the STARFISH/Shiga-like toxin I complex explains this activity. Two trisaccharide receptors at the tips of each of five spacer arms simultaneously engage all five B subunits of two toxin molecules. Shiga-like toxins are neutralized by tailored multivalent carbohydrate ligands.,Kitov PI, Sadowska JM, Mulvey G, Armstrong GD, Ling H, Pannu NS, Read RJ, Bundle DR Nature. 2000 Feb 10;403(6770):669-72. PMID:10688205 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Shiga toxin 3D structures

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