4m1u › Citations

The crystal structure of shiga toxin type 2 with bound disaccharide guides the design of a heterobifunctional toxin inhibitor.

Jacobson JM, Yin J, Kitov PI, Mulvey G, Griener TP, James MN, Armstrong G, Bundle DR
J Biol Chem 289 885-94 (2014)
Cited: 19 times
EuropePMC logo PMID: 24225957

Abstract

Shiga toxin type 2 (Stx2a) is clinically most closely associated with enterohemorrhagic E. coli O157:H7-mediated hemorrhagic colitis that sometimes progresses to hemolytic-uremic syndrome. The ability to express the toxin has been acquired by other Escherichia coli strains, and outbreaks of food poisoning have caused significant mortality rates as, for example, in the 2011 outbreak in northern Germany. Stx2a, an AB5 toxin, gains entry into human cells via the glycosphingolipid receptor Gb3. We have determined the first crystal structure of a disaccharide analog of Gb3 bound to the B5 pentamer of Stx2a holotoxin. In this Gb3 analog,-GalNAc replaces the terminal-Gal residue. This co-crystal structure confirms previous inferences that two of the primary binding sites identified in theB5 pentamer of Stx1 are also functional in Stx2a. This knowledge provides a rationale for the synthesis and evaluation of heterobifunctional antagonists for E. coli toxins that target Stx2a. Incorporation of GalNAc Gb3 trisaccharide in a heterobifunctional ligand with an attached pyruvate acetal, a ligand for human amyloid P component, and conjugation to poly[acrylamide-co-(3-azidopropylmethacrylamide)] produced a polymer that neutralized Stx2a in a mouse model of Shigatoxemia.

Reviews - 4m1u mentioned but not cited (2)

  1. Shiga Toxins: An Update on Host Factors and Biomedical Applications. Liu Y, Tian S, Thaker H, Dong M. Toxins (Basel) 13 222 (2021)
  2. Exploring multivalent carbohydrate-protein interactions by NMR. Quintana JI, Atxabal U, Unione L, Ardá A, Jiménez-Barbero J. Chem Soc Rev 52 1591-1613 (2023)

Articles - 4m1u mentioned but not cited (2)

  1. Glycolipid binding preferences of Shiga toxin variants. Karve SS, Weiss AA. PLoS One 9 e101173 (2014)
  2. The crystal structure of shiga toxin type 2 with bound disaccharide guides the design of a heterobifunctional toxin inhibitor. Jacobson JM, Yin J, Kitov PI, Mulvey G, Griener TP, James MN, Armstrong G, Bundle DR. J Biol Chem 289 885-894 (2014)


Reviews citing this publication (7)

  1. Shiga Toxins as Multi-Functional Proteins: Induction of Host Cellular Stress Responses, Role in Pathogenesis and Therapeutic Applications. Lee MS, Koo S, Jeong DG, Tesh VL. Toxins (Basel) 8 E77 (2016)
  2. Verotoxin Receptor-Based Pathology and Therapies. Lingwood C. Front Cell Infect Microbiol 10 123 (2020)
  3. Evolution and structural dynamics of bacterial glycan binding adhesins. Moonens K, Remaut H. Curr Opin Struct Biol 44 48-58 (2017)
  4. Do the A subunits contribute to the differences in the toxicity of Shiga toxin 1 and Shiga toxin 2? Basu D, Tumer NE. Toxins (Basel) 7 1467-1485 (2015)
  5. Polymer antidotes for toxin sequestration. Weisman A, Chou B, O'Brien J, Shea KJ. Adv Drug Deliv Rev 90 81-100 (2015)
  6. Role of Recent Therapeutic Applications and the Infection Strategies of Shiga Toxin-Producing Escherichia coli. Hwang SB, Chelliah R, Kang JE, Rubab M, Banan-MwineDaliri E, Elahi F, Oh DH. Front Cell Infect Microbiol 11 614963 (2021)
  7. Valid Presumption of Shiga Toxin-Mediated Damage of Developing Erythrocytes in EHEC-Associated Hemolytic Uremic Syndrome. Detzner J, Pohlentz G, Müthing J. Toxins (Basel) 12 E373 (2020)

Articles citing this publication (8)

  1. Research Support, Non-U.S. Gov't Virulence-targeted Antibacterials: Concept, Promise, and Susceptibility to Resistance Mechanisms. Ruer S, Pinotsis N, Steadman D, Waksman G, Remaut H. Chem Biol Drug Des 86 379-399 (2015)
  2. Recognition of human milk oligosaccharides by bacterial exotoxins. El-Hawiet A, Kitova EN, Klassen JS. Glycobiology 25 845-854 (2015)
  3. Structural and Functional Characterization of Stx2k, a New Subtype of Shiga Toxin 2. Hughes AC, Zhang Y, Bai X, Xiong Y, Wang Y, Yang X, Xu Q, He X. Microorganisms 8 E4 (2019)
  4. Tissue Responses to Shiga Toxin in Human Intestinal Organoids. Pradhan S, Karve SS, Weiss AA, Hawkins J, Poling HM, Helmrath MA, Wells JM, McCauley HA. Cell Mol Gastroenterol Hepatol 10 171-190 (2020)
  5. Addition of lysophospholipids with large head groups to cells inhibits Shiga toxin binding. Ailte I, Lingelem AB, Kavaliauskiene S, Bergan J, Kvalvaag AS, Myrann AG, Skotland T, Sandvig K. Sci Rep 6 30336 (2016)
  6. AB5 Preassembly Is Not Required for Shiga Toxin Activity. Pellino CA, Karve SS, Pradhan S, Weiss AA. J Bacteriol 198 1621-1630 (2016)
  7. Clustering of PK-trisaccharides on amphiphilic cyclodextrin reveals unprecedented affinity for the Shiga-like toxin Stx2. Zhang P, Paszkiewicz E, Wang Q, Sadowska JM, Kitov PI, Bundle DR, Ling CC. Chem Commun (Camb) 53 10528-10531 (2017)
  8. Synthetic investigation toward apigenin 5-O-glycoside camellianin B as well as the chemical structure revision. Hu Y, Tu YH, Liu DY, Liao JX, Sun JS. Org Biomol Chem 14 4842-4847 (2016)


Quick links