1qnu

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|PDB= 1qnu |SIZE=350|CAPTION= <scene name='initialview01'>1qnu</scene>, resolution 2.23&Aring;
|PDB= 1qnu |SIZE=350|CAPTION= <scene name='initialview01'>1qnu</scene>, resolution 2.23&Aring;
|SITE=
|SITE=
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|LIGAND= <scene name='pdbligand=EMB:METHYL-CARBAMIC+ACID+ETHYL+ESTER'>EMB</scene> and <scene name='pdbligand=MEC:ETHYL-CARBAMIC ACID METHYL ESTER'>MEC</scene>
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|LIGAND= <scene name='pdbligand=EMB:METHYL-CARBAMIC+ACID+ETHYL+ESTER'>EMB</scene>, <scene name='pdbligand=GAL:BETA-D-GALACTOSE'>GAL</scene>, <scene name='pdbligand=GLC:GLUCOSE'>GLC</scene>, <scene name='pdbligand=MEC:ETHYL-CARBAMIC+ACID+METHYL+ESTER'>MEC</scene>
|ACTIVITY=
|ACTIVITY=
|GENE=
|GENE=
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|DOMAIN=
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|RELATEDENTRY=
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1qnu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qnu OCA], [http://www.ebi.ac.uk/pdbsum/1qnu PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1qnu RCSB]</span>
}}
}}
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[[Category: Pannu, N S.]]
[[Category: Pannu, N S.]]
[[Category: Read, R J.]]
[[Category: Read, R J.]]
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[[Category: EMB]]
 
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[[Category: MEC]]
 
[[Category: multivalent protein-carbohydrate recognition]]
[[Category: multivalent protein-carbohydrate recognition]]
[[Category: ob-fold]]
[[Category: ob-fold]]
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[[Category: toxin]]
[[Category: toxin]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:40:16 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:16:28 2008''

Revision as of 20:16, 30 March 2008


PDB ID 1qnu

Drag the structure with the mouse to rotate
, resolution 2.23Å
Ligands: , , ,
Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



SHIGA-LIKE TOXIN I B SUBUNIT COMPLEXED WITH THE BRIDGED-STARFISH INHIBITOR


Overview

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.

About this Structure

1QNU is a Single protein structure of sequence from Bacteriophage h30, bacteriophaurce 3. Full crystallographic information is available from OCA.

Reference

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

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