Özet:

Cholera is a disease that is developed by parasitizing the bacteria called vibrio cholera in the small intestine of people and it causes severe watery diarrhea, if it is left untreated, it can result in death. The bacteria is transmitted to the people through the digestive tract with water and nutrients, starting with vomiting and going on with severe diarrhea. A potent enterotoxin, Cholera Toxin (CT) which is secreted by vibrio cholera is largely responsible for the disease. It first emerged in India and began to spread to the world between 1827-1975. The cause of the disease, Vibrio cholerae bacteria, which has been known since ancient times with high outbreaks and high mortality rates, has less resistance to external influences and dies in 10-15 minutes at 55°C and in 1-2 minutes at boiling temperature. They are not able to resist dryness, sunlight and acids. Gastric acidity inactivates the vibrations in a short time, which protects many people from being caught in cholera. ADP-Ribosylating Toxins (ADPRT), also including cholera toxin synthesized by this bacteria, are a large and potentially fatal toxin family. They are secreted by pathogenic bacteria and inhibit the functions of human target proteins. Based on structure-based multiple sequence alignments, the ADPRT family is classified into two groups according to the Nicotinamide Adenine Dinucleotide (NAD) that binds Diphtheria Toxin (DT) and CT. DT group toxins change eukaryotic elongation factor 2 and disrupt protein synthesis in eukaryotic cells. DT, exotoxin A (ETA) and cholix toxin are among the members of this group. CT group toxins target various essential proteins in host organisms. For example, CT and temperature-varying enterotoxin target Arg on Gs-R on G protein. This leads to uncontrolled adenylate cyclase activity. Although ADPRT enzymes exhibit a variety of functions and low sequence identities, they share common structural and functional characteristics. This toxin family has the ability to catalyze NAD by using the same pathway with poly ADP-ribose polymerases. We think that being clarified as a matter of the cholera toxin structure, which is the member of this family, will play an important role in the development of many drug design studies such as being able to interfere in significant proteins structure for cancer cells and the development of various catalysis mechanisms. In this study, we investigated the three-dimensional structure of cholera toxin, which is an important member of the ADPRT family, and the interface which will interact with the other amino acids whose binding energies are higher than other amino acids which are situated in the structure (hot spot) by using theoretical and experimental methods. As a result of our theoretical and experimental studies we think that the 12 amino acid sequence of Cholera toxin, constituting the common structural region that binds to NAD in the ADP-ribosylating toxins family is the sequence of 61- STSISLRSAHLV-72.

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