Structural toxin

LP Vernon, JD Bell. Membrane structure, toxins and phospholipase A2 activity. Pharmacol Ther 54 269-295, 1992. 

Page 1170 (Figure 28 5) is adapted from crystallographic coordinates deposited with the Protein Data Bank PDB ID IDDN White A Ding X Vanderspek J C Murphy J R Ringe D Structure of the Metal Ion Activated Diphtheria Toxin Re pressor/Tox Operator Complex Nature 394 p 502 (1998)... 

In vitro cytotoxicity assays using isolated cells have been applied intermittently to cyanobacterial toxicity testing over several years." Cells investigated for suitability in cyanobacterial toxin assays include primary liver cells (hepatocytes) isolated from rodents and fish, established permanent mammalian cell lines, including hepatocytes, fibroblasts and cancerous cells, and erythrocytes. Earlier work suggested that extracts from toxic cyanobacteria disrupted cells of established lines and erythrocytes," but studies with purified microcystins revealed no alterations in structure or ion transport in fibroblasts or erythrocytes,... 

FIGURE 10.32 The structures of (a) S-eudotoxiu (two views) from Bacillus thuringiensis and (b) diphtheria toxin from Cmynehacterium diphtheriae. Each of these toxins possesses a bundle of a-hehces which is presumed to form the trausmembraue channel when the toxin Is Inserted across the host membrane. In S-endotoxln, helix 5 (white) Is surrounded by 6 helices (red) In a 7-hellx bundle. In diphtheria toxin, three hydrophobic helices (white) lie at the center of the transmembrane domain (red). 

All of the transport systems examined thus far are relatively large proteins. Several small molecule toxins produced by microorganisms facilitate ion transport across membranes. Due to their relative simplicity, these molecules, the lonophore antibiotics, represent paradigms of the mobile carrier and pore or charmel models for membrane transport. Mobile carriers are molecules that form complexes with particular ions and diffuse freely across a lipid membrane (Figure 10.38). Pores or channels, on the other hand, adopt a fixed orientation in a membrane, creating a hole that permits the transmembrane movement of ions. These pores or channels may be formed from monomeric or (more often) multimeric structures in the membrane. 

Li, J., Carroll, J., and Ellar, D., 1991. Cry.stal. structure of in.secticidal 5-endo-toxin from Bacillus thuringiensis at 2.5 A resolution. Nature 353 815-821. 

Parker, M., Buckley, J., Postma, J., et al., 1994. Structure of the Aeromonas toxin proaerolysin in its water-soluble and membrane-channel states. Nature 367 292-295. 

Petosa, C., Collier, R., Klimpel, K, et al., 1997. Crystal structure of die andir2LX toxin protecdve andgen. Nature 385 833-838. 

As an example of the fascinating current progress, Dr. Spencer will describe a beautiful piece of research on the isolation and structure proof of the toxin from Helminthosporium sativum, an important... 

The toxin kills larvae and/or pupae of some Diptera and Lepidoptera and acts primarily by prevention of completion of pupation. It is produced in cultures prior to sporulation (9,26) and remains in the supernatant liquid of sporulated cultures. Its chemical structure is not known, but initial isolation and purification studies are under way (9). One cannot, however, leave a discussion of this toxin with a feeling of certainty. Burgerjon and deBarjac (7) and Krieg and Herfs (20) reported the above-mentioned effectiveness of the soluble... 

The toxin is less effective on oats and wheat and does not have the specificity reported for the toxin from Hehmnthosporium vic-toriae for oats. A metabolite isolated from another strain of H. sativum in Japan by Tamura et al. (15) has a marked elongation effect on the shoots of rice seedlings. The structure of this metabolite is closely related to that described here. 

Another subfamily of ADP-iibosylating toxins modifies G-actin (at Argl77), thereby inhibiting actin polymerization. Members of this family are, for example, C. botulinum C2 toxin and Clostridium perfringens iota toxin. These toxins are binary in structure. They consist of an enzyme component and a separate binding component, which is structurally related to the binding component of anthrax toxin [3]. 

Allingham JS, Zampella A, D Auria MV et al (2005) Structures of microfilament destabilizing toxins bound to actin provide insight into toxin design and activity. Proc Natl Acad Sci USA 102 14527-14532... 

The vesicular monoamine transporters (VMATs) were identified in a screen for genes that confer resistance to the parkinsonian neurotoxin MPP+ [2]. The resistance apparently results from sequestration of the toxin inside vesicles, away from its primary site of action in mitochondria. In addition to recognizing MPP+, the transporter s mediate the uptake of dopamine, ser otonin, epinephrine, and norepinephrine by neurons and endocrine cells. Structurally, the VMATs show no relationship to plasma membrane monoamine transporters. 

Figure 5.59 Molecular structures of the diarrhetic shellfish poisons (a) pectenotoxin-6 (PTX6) (b) okadaic acid (OA) (c) dinophysistoxin-1 (DTXl) (d) yessotoxin (YTX). Reprinted from J. Chromatogr., A, 943, Matrix effect and correction by standard addition in quantitative liquid chromatographic-mass spectrometric analysis of diarrhetic shellfish poisoning toxins , Ito, S. and Tsukada, K., 39-46, Copyright (2002), with permission from Elsevier Science.

Structures of spider toxins that antagonise insect muscle glutamate receptors (and glutamate receptors of other animals)... 

---