Virulent infectious diseases caused by bacteria have in the past caused widespread epidemics. In the middle ages an epidemic of the bubonic plague, also called the black death for its clinical symptoms, and caused by the bacterium Yersinia pestis, killed roughly half of the population of medieval Europe in about two years. Diphtheria, caused by Corynebacterium diphtheriae, is another example. In many cases the responsible bacteria have been almost eradicated, either by the development of effective vaccines for diphtheria, or by improvement of sanitary conditions which eliminate breeding grounds for these bacteria. Nevertheless, other disease causing bacteria still continue to thrive, especially in third-world countries, caused by poor sanitary conditions. In some cases stocks of such bacteria have been kept deliberately as potential biological weapons. One such disease causing bacterium is Vibrio cholerae. It causes a disease called cholera. After for instance the drinking of water contaminated with V. cholerae, these bacteria reproduced in the gut. There they release a potent toxin, called cholera toxin. This toxin binds to the surface of epithelial cells lining the gut surface. After successful binding to these cells the toxin is cleaved chemically and one part of the toxin enters the interior of the cell. Once inside the cell, this toxin fragment catalyzes ADP ribosylation of GTP binding protein and disrupts the normal cell cycle. Often the symptoms of cholera are mild, but in severe cases of the disease massive amounts of water and sodium are released into the gut and the resulting diarrhea often produces more to 6 liters of liquid per hour. This diarrhea leads to a drastic loss of fluids and salts with devastating dehydration of the affected individual and may result in death, unless the dehydration is properly treated. Cholera toxin, is an AB5 type toxin.
The toxin is made from six building blocks, one subunit of type A and five subunits of type B. The five B subunits are arranged if a pentameric ring and on their surface have a biding site for certain types of sugar chains attached to cell surfaces. On the opposite site of this ring sits the A subunit. It consists of two parts, the actual enzyme A1 and a short piece of polypeptide, A2, which attaches itself to the B pentamer. The peptide link between A1 and A2 is cut by a peptidase and they then are held together by a disulfide bond. Prior to entering the cell this disulfide bond is broken and the A1 unit passes through the cell membrane into the cell interior. Diphtheria toxin, which produces cell death in a fashion similar to cholera toxin, has a different structure, of AB type, obtaining only one binding domain.
Protein Data Bank (PDB)