Properties toxins

Zigmond, 1988). The ATP-hydrolysis that accompanies actin polymerization, ATP —> ADP + Pj, and the subsequent release of the cleaved phosphate (Pj) are believed to act as a clock (Pollard et ah, 1992 Allen et ah, 1996), altering in a time-dependent manner the mechanical properties of the filament and its propensity to depolymerize. Molecular dynamics simulations suggested a so-called back door mechanism for the hydrolysis reaction ATP ADP - - Pj in which ATP enters the actin from one side, ADP leaves from the same side, but Pj leaves from the opposite side, the back door (Wriggers and Schulten, 1997b). This hypothesis can explain the effect of the toxin phalloidin which blocks the exit of the putative back door pathway and, thereby, delays Pi release as observed experimentally (Dancker and Hess, 1990). 

The detection and quantification of cyanobacterial toxins quoted in the above examples required methods which have been undergoing rapid development in recent years, and as the need for greater understanding of the properties and occurrence of the toxins continues to grow, these are continuing to be developed. This has resulted in methods of cyanobacterial toxin detection which are more sensitive, quantitative, reliable, specific and humane. Many of these methods are presented and discussed in the proceedings of a recent conference. 

The common hemlock, Conium maculatum, contain five alkaloids. Power and Tutin found a similar mixture in fool s parsley, and a volatile alkaloid resembling coniine i.s stated to occur in certain aroids. According to Svagr, water hemlock Cicuta virosa) owes its poisonous properties to toxin and not to cicutine, a name sometimes used as a synonym for coniine. The toxic properties of hemlock juice have been known ftom very early times thus it was the chief ingredient in the poison administered to criminals by the Greeks. The leaves and the unripe fruits are the parts used in medicine. The following are the names and formulae of the alkaloids —... 

G. A. Codd, Cyanobacterial toxins occuixance, properties and biological significance . WaterSci. Technol. 32 149-156(1995). 

In summary, analyses for the saxitoxins provide information that, in principle, is clear and readily interpreted while the design and interpretation of assays for the saxitoxins is complicate by the multiplicity of the toxins, their differing properties, and the variations in toxin composition that will be encountered. Assays, however, can in principle be very simple to perform while the presently available analyses for the saxitoxins require fairly complex equipment. 

Anatoxin-a has already proven its usefulness as a research tool in our laboratories. It is facilitating the understanding of the biophysical properties of the AChR and of the localization of the AChR in the CNS. The toxin or derivatives of it could be useful therapeutically in diseases of nicotinic receptor pathology (myasthenia gravis or Alzheimer s disease), because as a secondary amine (+)-anatoxin-a can penetrate into the CNS. 

Three classes of polyethers, okadaic acid derivatives, pectenotoxins, and yessotoxin were isolated from bivalves in connection with diarrhetic shellfish poisoning. The etiology of the toxins, toxicological properties, and determination methods are described. 

Palytoxin is probably one of the most potent toxins known to humans. Intravenous LD q values in the sue species that have been studied are consistently less than 0.5 ig/kg. In addition, palytoxin possesses a speed of action and other pharmacologic properties that are markedly different from those exhibited by other toxic materials. For example, when injected iv or sc, palytoxin is extremely toxic yet when given po or ir, it is relatively non-toxic. It is also very interesting that the doses of palytoxin required to kill are somewhat different in anesthetized vs. unanesthetized animals. 

Despite the vast amount of data on the pharmacological properties, very little about the conformation of the proteins has b n known until recent NMR studies. 2D-NMR results have provided detailed information about the secondary structure of several related anemone toxins. ATX I from Anemonia sulcata (3,4) and AP-A from Anthopleura xanthogrammica (5,6) have been studied by Gooley and Norton, and more recently Widmer et al. have further purified the A. sulcata toxins and obtained complete sequence specific assignments for ATX la (7). Our laboratory, on the other hand, has studied the structures of RpII and RpIII from RadiarUhiis paumotensis (8). 

Schweitz et al. purified four related toxins (Rpl, RpII, RpIII, and RpIV) from sea anemone Radianthus paumotensis (Rp) and studied their pharmacological properties (9). During the course of initial NMR studies, the reported sequence of RpII was found to have errors, and was redetermined (8). Subsequently Metrione et al. determined the sequence of RpIII as well (10). T e other two Rp toxin sequences are yet to be determined. Sequences of the Rp, and several other sea anemone toxins, are shown in Table I. We have used a two letter code to denote the species consistently and this notation differs from the earlier designations of Norton and Wiithrich groups. In our notation. As la and Ax I correspond to ATX la and AP-A, respectively. From alignment of the cystines in these sequences, it is clear that Rp toxins have three disulfide bonds, as do the other toxins. 

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