Journal of Applied Biomedicine 1: 141–147, 2003 ISSN 1214-0287 Plant toxic proteins and their current significance for warfare and medicine Jiří Patočka 1 and Ladislav Středa 2 1 Department of Toxicology, Military Medical Academy, Hradec Králové and Faculty of Health and Social Studies, University of South Bohemia, České Budějovice, Czech Republic 2 Department for Control of the Prohibition of Chemical and Biological Weapons, State Office for Nuclear Safety, Praha, Czech Republic Summary Abrin, ricin, viscumin, modeccin, and volkensin are very potent toxins derived from plants. They are glycoproteins composed of two polypeptide chains linked by a disulphide bridge. The A-chain is the enzymatic toxic moiety and B-chain is responsible for bonding to the target cell and internalization of toxin. The toxic part of the toxin molecule removes an adenine from a specific adenosine residue in ribosomal RNA and block proteosynthesis. That is the reason of extreme toxicity of these compounds and their capacity to be used as biological warfare agents or terrorist weapon. Therefore all these compounds are in the schedules of controlled biological agents and toxins. Contrariwise, plant ribosome-inactivating proteins are studied intensive as possible chemotherapeutic agents. Keywords: plant toxic proteins – ribosome inactivating proteins – abrin – ricin – modeccin – viscumin – volkensin – warfare – medicine INTRODUCTION Many organisms produce potently toxic proteins that act on other cells, sometimes with lethal effects. In this way, such proteins help to increase the chance of survival or proliferation of the producing organism. Some of them have an exquisitely specific action. For example ricin and ricin-like proteins have evolved to selectively target ribosomes within the cells of susceptible organisms, thereby enabling a fatal disruption of protein synthesis. These particular toxins are able to exploit intracellular transport pathways to travel from the cell surface to their substrates in the cytosol. Plant toxic proteins belong to a group of phytotoxins, which inhibit the protein synthesis of eukaryotic cells. The toxins of this group are glycoproteins with molecular weights of about 60 kDa which consist of two subunits linked into a dimer by a disulfide bond. One of the subunits is lectin with sites for carbohydrate binding (B-chain), and the other subunit is specific N- glycosidase (A-chain), which modifies the 28S rRNA-60S ribosomal subunit. The group of proteins known as the lectins was first recognised in plant seeds and they bind to specific sugars. Although lectins, in general, are not very toxic, there are some relationships between lectins and toxins (Wang and Xu 2000). They may also serve as recognition markers in cellular differentiation and act as immunotoxin. Only A-chain is toxic due to inhibiting protein synthesis. The A-chain catalytically inactivates 60S ribosomal subunit by removing adenine from positions 4 and 324 of 28S rRNA. Ribosome-inactivating proteins (RIP) have been identified in many plants and some of them are very toxic, but only in connection with B-chain. The A-chain is carrier of toxicity, but B-chain binds to cell surface receptors and facilitate a transport of the A-chain across the cell membrane. The A-chain is not active until it is internalized by the cell, where halts protein synthesis. Each toxin molecule can disable approximately 2000 polysomes per minute, enough to eventually kill the cell. The most known plant toxic proteins of this type are ricin, abrin, modeccin, viscumin and volkensin. Likewise act some bacterial protein toxins, for instance diphteria