3mxg

Structure of Shiga Toxin type 2 (Stx2) B Pentamer Mutant Q40L

spinqualitylabelsall models 3mxg, resolution 2.49Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3mxg is a 10 chain structure with sequence from Eco57. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: XLS Gene: stx2B, L0104 (ECO57) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Escherichia coli strain O157:H7 is a major cause of food poisoning that can result in severe diarrhea and, in some cases, renal failure. The pathogenesis of E. coli O157:H7 is in large part due to the production of Shiga toxin (Stx), an AB(5) toxin that consists of a ribosomal RNA-cleaving A-subunit surrounded by a pentamer of receptor-binding B subunits. There are two major isoforms, Stx1 and Stx2, which differ dramatically in potency despite having 57% sequence identity. Animal studies and epidemiological studies show Stx2 is associated with more severe disease. Although the molecular basis of this difference is unknown, data suggest it is associated with the B-subunit. Mass spectrometry studies have suggested differential B-pentamer stability between Stx1 and Stx2. We have examined the relative stability of the B-pentamers in solution. Analytical ultracentrifugation using purified B-subunits demonstrates that Stx2B, the more deadly isoform, shows decreased pentamer stability compared to Stx1B (EC(50) = 2.3 microM vs. EC(50) = 0.043 microM for Stx1B). X-ray crystal structures of Stx1B and Stx2B identified a glutamine in Stx2 (versus leucine in Stx1) within the otherwise strongly hydrophobic interface between B-subunits. Interchanging these residues switches the stability phenotype of the B-pentamers of Stx1 and Stx2, as demonstrated by analytical ultracentrifugation and circular dichroism. These studies demonstrate a profound difference in stability of the B-pentamers in Stx1 and Stx2, illustrate the mechanistic basis for this differential stability, and provide novel reagents to test the basis for differential pathogenicity of these toxins. Molecular basis of differential B-pentamer stability of Shiga toxins 1 and 2.,Conrady DG, Flagler MJ, Friedmann DR, Vander Wielen BD, Kovall RA, Weiss AA, Herr AB PLoS One. 2010 Dec 28;5(12):e15153. PMID:21203383 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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