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Chemical Compound Review

Exotoxin     2-[5-[[5-(6-aminopurin-9-yl)- 3,4-dihydroxy...

Synonyms: Thurintox, Thuringiensin, Turingin-1, AG-E-68728, SureCN5934015, ...
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Disease relevance of Exotoxin

  • Pseudomonas aeruginosa exotoxin A [1].
  • Functional domains of Pseudomonas exotoxin identified by deletion analysis of the gene expressed in E. coli [2].
  • Strains of group A beta-hemolytic streptococci isolated from 10 patients were not of a single M or T type; however, 8 of the 10 strains produced pyrogenic exotoxin A (scarlet fever toxin A, a classic erythrogenic toxin), which has rarely been observed in recent years [3].
  • A newly devised conjugate of the capsular polysaccharide of Salmonella typhi, Vi, bound to nontoxic recombinant Pseudomonas aeruginosa exotoxin A (rEPA), has enhanced immunogenicity in adults and in children 5 to 14 years old and has elicited a booster response in children 2 to 4 years old [4].
  • The toxic shock syndrome exotoxin structural gene is not detectably transmitted by a prophage [5].

Psychiatry related information on Exotoxin


High impact information on Exotoxin


Chemical compound and disease context of Exotoxin


Biological context of Exotoxin

  • Exotoxin A also prevented the transporter associated with antigen processing (TAP) inhibitor, ICP47, from entering the cytosol and blocking TAP-mediated peptide transport [16].
  • Exogenous Pseudomonas aeruginosa Exotoxin A, which inhibits protein translocation from the ER to the cytosol, abrogated crosspresentation [16].
  • Amino acid sequence analysis and immunological reactivity suggest NPBP is the streptococcal pyrogenic exotoxin B precursor, also previously described as zymogen (streptococcal proteinase precursor) [17].
  • We exploited knowledge of genetic diversity and relationships among exotoxin A-producing patient strains provided by multilocus enzyme electrophoresis to select strains for comparative sequencing of toxin genes [18].
  • An MDA-468 subline selected after long-term treatment with a TGF-alpha-Pseudomonas exotoxin A fusion protein 40 lacked EGF binding and also exhibited cisplatin resistance (1-hour IC50: > 30 microM) compared with parental cells [19].

Anatomical context of Exotoxin


Associations of Exotoxin with other chemical compounds

  • C3 exotoxin induced the retraction of filopodia, the disappearance of focal complexes, and a global decrease in the F-actin content of J774 cells [25].
  • Streptolysin O (SLO) is a bacterial exotoxin that binds to cell membranes containing cholesterol and then oligomerizes to form large pores [26].
  • CM101, a bacterial polysaccharide exotoxin produced by group B Streptococcus (GBS), also referred to as GBS toxin, has been shown to target pathological neovasculature and activate complement (C3), thereby inducing neovascularitis, infiltration of inflammatory cells, inhibition of tumor growth, and apoptosis in murine tumor models [27].
  • This exotoxin derivative, missing domain I and referred to as LysPE40, is made up of a 13-kilodalton NH2-terminal translocation domain II connected by a segment of 40 amino acids to enzyme domain III of the toxin, a 23-kilodalton ADP-ribosyltransferase [28].
  • The exotoxin was purified from cell-free culture supernatant fluids by using differential precipitation with ethanol and resolubilization in pyrogen-free distilled water followed by preparative thin-layer isoelectric focusing [29].

Gene context of Exotoxin


Analytical, diagnostic and therapeutic context of Exotoxin


  1. Pseudomonas aeruginosa exotoxin A. Pollack, M. N. Engl. J. Med. (1980) [Pubmed]
  2. Functional domains of Pseudomonas exotoxin identified by deletion analysis of the gene expressed in E. coli. Hwang, J., Fitzgerald, D.J., Adhya, S., Pastan, I. Cell (1987) [Pubmed]
  3. Severe group A streptococcal infections associated with a toxic shock-like syndrome and scarlet fever toxin A. Stevens, D.L., Tanner, M.H., Winship, J., Swarts, R., Ries, K.M., Schlievert, P.M., Kaplan, E. N. Engl. J. Med. (1989) [Pubmed]
  4. The efficacy of a Salmonella typhi Vi conjugate vaccine in two-to-five-year-old children. Lin, F.Y., Ho, V.A., Khiem, H.B., Trach, D.D., Bay, P.V., Thanh, T.C., Kossaczka, Z., Bryla, D.A., Shiloach, J., Robbins, J.B., Schneerson, R., Szu, S.C. N. Engl. J. Med. (2001) [Pubmed]
  5. The toxic shock syndrome exotoxin structural gene is not detectably transmitted by a prophage. Kreiswirth, B.N., Löfdahl, S., Betley, M.J., O'Reilly, M., Schlievert, P.M., Bergdoll, M.S., Novick, R.P. Nature (1983) [Pubmed]
  6. Autopsy findings in an outbreak of severe systemic illness in heroin users following injection site inflammation: an effect of Clostridium novyi exotoxin? Finn, S.P., Leen, E., English, L., O'Briain, D.S. Arch. Pathol. Lab. Med. (2003) [Pubmed]
  7. Two-component regulator of Enterococcus faecalis cytolysin responds to quorum-sensing autoinduction. Haas, W., Shepard, B.D., Gilmore, M.S. Nature (2002) [Pubmed]
  8. Structural basis for the activation of anthrax adenylyl cyclase exotoxin by calmodulin. Drum, C.L., Yan, S.Z., Bard, J., Shen, Y.Q., Lu, D., Soelaiman, S., Grabarek, Z., Bohm, A., Tang, W.J. Nature (2002) [Pubmed]
  9. Crystal structure of a cholera toxin-related heat-labile enterotoxin from E. coli. Sixma, T.K., Pronk, S.E., Kalk, K.H., Wartna, E.S., van Zanten, B.A., Witholt, B., Hol, W.G. Nature (1991) [Pubmed]
  10. Selective killing of HIV-infected cells by recombinant human CD4-Pseudomonas exotoxin hybrid protein. Chaudhary, V.K., Mizukami, T., Fuerst, T.R., FitzGerald, D.J., Moss, B., Pastan, I., Berger, E.A. Nature (1988) [Pubmed]
  11. Leukocytosis and resistance to septic shock in intercellular adhesion molecule 1-deficient mice. Xu, H., Gonzalo, J.A., St Pierre, Y., Williams, I.R., Kupper, T.S., Cotran, R.S., Springer, T.A., Gutierrez-Ramos, J.C. J. Exp. Med. (1994) [Pubmed]
  12. Protective activity of antibodies to exotoxin A and lipopolysaccharide at the onset of Pseudomonas aeruginosa septicemia in man. Pollack, M., Young, L.S. J. Clin. Invest. (1979) [Pubmed]
  13. Specific disruption of vimentin filament organization in monkey kidney CV-1 cells by diphtheria toxin, exotoxin A, and cycloheximide. Sharpe, A.H., Chen, L.B., Murphy, J.R., Fields, B.N. Proc. Natl. Acad. Sci. U.S.A. (1980) [Pubmed]
  14. Elimination of infectious human immunodeficiency virus from human T-cell cultures by synergistic action of CD4-Pseudomonas exotoxin and reverse transcriptase inhibitors. Ashorn, P., Moss, B., Weinstein, J.N., Chaudhary, V.K., FitzGerald, D.J., Pastan, I., Berger, E.A. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  15. Enhancement of cytotoxicities of ricin and Pseudomonas toxin in Chinese hamster ovary cells by nigericin. Ray, B., Wu, H.C. Mol. Cell. Biol. (1981) [Pubmed]
  16. A Role for the Endoplasmic Reticulum Protein Retrotranslocation Machinery during Crosspresentation by Dendritic Cells. Ackerman, A.L., Giodini, A., Cresswell, P. Immunity (2006) [Pubmed]
  17. Identification of an extracellular plasmin binding protein from nephritogenic streptococci. Poon-King, R., Bannan, J., Viteri, A., Cu, G., Zabriskie, J.B. J. Exp. Med. (1993) [Pubmed]
  18. Characterization and clonal distribution of four alleles of the speA gene encoding pyrogenic exotoxin A (scarlet fever toxin) in Streptococcus pyogenes. Nelson, K., Schlievert, P.M., Selander, R.K., Musser, J.M. J. Exp. Med. (1991) [Pubmed]
  19. Abrogation of cisplatin-induced programmed cell death in human breast cancer cells by epidermal growth factor antisense RNA. Dixit, M., Yang, J.L., Poirier, M.C., Price, J.O., Andrews, P.A., Arteaga, C.L. J. Natl. Cancer Inst. (1997) [Pubmed]
  20. Inhibition of Fc receptors on a murine lymphoid cell line by cholera exotoxin. Zuckerman, S.H., Doublas, S.D. Nature (1975) [Pubmed]
  21. Action of Corynebacterium ovis exotoxin on endothelial cells of blood vessels. Carne, H.R., Onon, E.O. Nature (1978) [Pubmed]
  22. The superantigen streptococcal pyrogenic exotoxin C (SPE-C) exhibits a novel mode of action. Li, P.L., Tiedemann, R.E., Moffat, S.L., Fraser, J.D. J. Exp. Med. (1997) [Pubmed]
  23. T cell-mediated lethal shock triggered in mice by the superantigen staphylococcal enterotoxin B: critical role of tumor necrosis factor. Miethke, T., Wahl, C., Heeg, K., Echtenacher, B., Krammer, P.H., Wagner, H. J. Exp. Med. (1992) [Pubmed]
  24. The staphylococcal toxic shock syndrome toxin 1 triggers B cell proliferation and differentiation via major histocompatibility complex-unrestricted cognate T/B cell interaction. Mourad, W., Scholl, P., Diaz, A., Geha, R., Chatila, T. J. Exp. Med. (1989) [Pubmed]
  25. Rho is required for the initiation of calcium signaling and phagocytosis by Fcgamma receptors in macrophages. Hackam, D.J., Rotstein, O.D., Schreiber, A., Zhang, W., Grinstein, S. J. Exp. Med. (1997) [Pubmed]
  26. Assembly mechanism of the oligomeric streptolysin O pore: the early membrane lesion is lined by a free edge of the lipid membrane and is extended gradually during oligomerization. Palmer, M., Harris, R., Freytag, C., Kehoe, M., Tranum-Jensen, J., Bhakdi, S. EMBO J. (1998) [Pubmed]
  27. CM101 treatment overrides tumor-induced immunoprivilege leading to apoptosis. Yakes, F.M., Wamil, B.D., Sun, F., Yan, H.P., Carter, C.E., Hellerqvist, C.G. Cancer Res. (2000) [Pubmed]
  28. Proteases from human immunodeficiency virus and avian myeloblastosis virus show distinct specificities in hydrolysis of multidomain protein substrates. Tomasselli, A.G., Hui, J.O., Sawyer, T.K., Staples, D.J., Bannow, C.A., Reardon, I.M., Chaudhary, V.K., Fryling, C.M., Pastan, I., Fitzgerald, D.J. J. Virol. (1990) [Pubmed]
  29. Purification and characterization of staphylococcal pyrogenic exotoxin type B. Schlievert, P.M. Biochemistry (1980) [Pubmed]
  30. Targeting of interleukin-13 receptor on human renal cell carcinoma cells by a recombinant chimeric protein composed of interleukin-13 and a truncated form of Pseudomonas exotoxin A (PE38QQR). Puri, R.K., Leland, P., Obiri, N.I., Husain, S.R., Kreitman, R.J., Haas, G.P., Pastan, I., Debinski, W. Blood (1996) [Pubmed]
  31. Purging of mammary carcinoma cells during ex vivo culture of CD34+ hematopoietic progenitor cells with recombinant immunotoxins. Spyridonidis, A., Schmidt, M., Bernhardt, W., Papadimitriou, A., Azemar, M., Wels, W., Groner, B., Henschler, R. Blood (1998) [Pubmed]
  32. Structure, function, and targeting of interleukin 4 receptors on human head and neck cancer cells. Kawakami, K., Leland, P., Puri, R.K. Cancer Res. (2000) [Pubmed]
  33. Small chimeric toxins containing only transforming growth factor alpha and domain III of Pseudomonas exotoxin with good antitumor activity in mice. Kihara, A., Pastan, I. Cancer Res. (1994) [Pubmed]
  34. Glycoprotein 330, a member of the low density lipoprotein receptor family, binds lipoprotein lipase in vitro. Kounnas, M.Z., Chappell, D.A., Strickland, D.K., Argraves, W.S. J. Biol. Chem. (1993) [Pubmed]
  35. Efficacy of the anti-CD22 recombinant immunotoxin BL22 in chemotherapy-resistant hairy-cell leukemia. Kreitman, R.J., Wilson, W.H., Bergeron, K., Raggio, M., Stetler-Stevenson, M., FitzGerald, D.J., Pastan, I. N. Engl. J. Med. (2001) [Pubmed]
  36. Respiratory infections with Pseudomonas aeruginosa in children with cystic fibrosis: early detection by serology and assessment of risk factors. West, S.E., Zeng, L., Lee, B.L., Kosorok, M.R., Laxova, A., Rock, M.J., Splaingard, M.J., Farrell, P.M. JAMA (2002) [Pubmed]
  37. Monoclonal antibody C242-Pseudomonas exotoxin A. A specific and potent immunotoxin with antitumor activity on a human colon cancer xenograft in nude mice. Debinski, W., Karlsson, B., Lindholm, L., Siegall, C.B., Willingham, M.C., FitzGerald, D., Pastan, I. J. Clin. Invest. (1992) [Pubmed]
  38. A rapid method of cloning functional variable-region antibody genes in Escherichia coli as single-chain immunotoxins. Chaudhary, V.K., Batra, J.K., Gallo, M.G., Willingham, M.C., FitzGerald, D.J., Pastan, I. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  39. Inhibition of antibody response to Pseudomonas exotoxin and an immunotoxin containing Pseudomonas exotoxin by 15-deoxyspergualin in mice. Pai, L.H., FitzGerald, D.J., Tepper, M., Schacter, B., Spitalny, G., Pastan, I. Cancer Res. (1990) [Pubmed]
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