1R4P: Shiga Toxin Type 2

Citation:
Abstract
Several serotypes of Escherichia coli produce protein toxins closely related to Shiga toxin (Stx) from Shigella dysenteriae serotype 1. These Stx-producing E. coli cause outbreaks of hemorrhagic colitis and hemolytic uremic syndrome in humans, with the latter being more likely if the E. coli produce Stx2 than if they only produce Stx1. To investigate the differences among the Stxs, which are all AB(5) toxins, the crystal structure of Stx2 from E. coli O157:H7 was determined at 1.8-A resolution and compared with the known structure of Stx. Our major finding was that, in contrast to Stx, the active site of the A-subunit of Stx2 is accessible in the holotoxin, and a molecule of formic acid and a water molecule mimic the binding of the adenine base of the substrate. Further, the A-subunit adopts a different orientation with respect to the B-subunits in Stx2 than in Stx, due to interactions between the carboxyl termini of the B-subunits and neighboring regions of the A-subunit. Of the three types of receptor-binding sites in the B-pentamer, one has a different conformation in Stx2 than in Stx, and the carboxyl terminus of the A-subunit binds at another. Any of these structural differences might result in different mechanisms of action of the two toxins and the development of hemolytic uremic syndrome upon exposure to Stx2.
PDB ID: 1R4PDownload
MMDB ID: 27700
PDB Deposition Date: 2003/10/7
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 1.77  Å
Source Organism:
Similar Structures:
Biological Unit for 1R4P: hexameric; determined by author and by software (PISA)
Molecular Components in 1R4P
Label Count Molecule
Proteins (6 molecules)
1
Shiga-like Toxin Type II a Subunit
Molecule annotation
5
Shiga-like Toxin Type II B Subunit
Molecule annotation
Chemicals (29 molecules)
1
5
2
5
3
15
4
4
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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