Structures of toxin

Numerous organisms, both marine and terrestrial, produce protein toxins. These are typically relatively small, and rich in disulfide crosslinks. Since they are often difficult to crystallize, relatively few structures from this class of proteins are known. In the past five years two dimensional NMR methods have developed to the point where they can be used to determine the solution structures of small proteins and nucleic acids. We have analyzed the structures of toxins II and III of RadiarUhus paumotensis using this approach. We find that the dominant structure is )9-sheet, with the strands connected by loops of irregular structure. Most of the residues which have been determined to be important for toxicity are contained in one of the loops. The general methods used for structure analysis will be described, and the structures of the toxins RpII and RpIII will be discussed and compared with homologous toxins from other anemone species. 

Chemical techniques for the isolation, purification and elucidation of the structure of toxins have evolved to the extent that it is frequently a routine procedure to identify the chemical nature of a newly discovered toxin once it has been purified, although difficulties arise when the toxin is a very large polypeptide, protein, or a very complex organic molecule. However, it is sometimes found that a toxin becomes progressively more labile and stabilizing contaminants are removed by the purification processes. An example of this is Cyanea toxic material which becomes increasingly labile with each purification step 111). 

Regardless of the true role of channel formation in productive internalization, it is fascinating that microbial toxins, which presumably are ancient molecules, have this property. It is inevitable that investigators will compare the molecular biology and structure of toxin channels with corresponding properties of endogenous channels (e.g. sodium or potassium), and from this deduce something about the evolution of channels. 

The ELISA is currently the most promising method for rapid sample screening for MCs because of its sensitivity, specificity, and ease of operation. These assays are based on the use of monoclonal or polyclonal antibodies. These assays show greater specificity than protein phosphatase inhibition assays but do not indicate the relative toxicides of microcystin and nodularin variants instead, ELISAs rely on the structure of toxins for detection. Therefore cross-reactivities of the different toxins may vary and sensitivity depends on the structure rather than toxicity. 

Bamburg JR, Riggs NV, Strong EM (1968) The Structures of Toxins from Two Strains of Fusarium tricinctum. Tetrahedron 24 3329... 

Bamburg, J.R., Riggs, N.V. and Strong, F.M. (1968). The structures of toxins from two strains of Fusarium tricinctum. Tetrahedron 3329-3336. 

Blumenthal, K.M., P.S. Keim, R.L. Heinrikson, and W.R. Kem Structure and Action of Heteronemertine Polypeptide Toxins. Amino Acid Sequence of Cerebratulus lacteus Toxin B-II and Revised Structure of Toxin B-IV. J. Biol. Chem. 256, 9063 (1981). 

To investigate die chemical functionality of the toxin, we converted compound 1 to stable and nonvolatile derivative 2 by reaction widi diphenyldiazomediane (3) (Fig. la. Supplementary Methods and Supplementaiy Figs. 5 and 6 online). We established the structure of 2 by H NMR, C NMR, MS and IR spectra, which also confirmed the structure of toxin 1. 

The second section contains articles on the origin and structure—function aspects of toxins. An understanding of the structure of toxins and the relationship between structure and function has always been a fascinating topic. However, recent advances in the tools available for the structure determination as well as for structure alteration are moving the field of toxin research at a much faster pace than in the past. This is obviously reflected in the number of chapters in this section of the book. 

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