Corynebacterium diphtheria is a wide-spread bacterium in nature, which causes diphtheria in humans. Diphtheria toxin (DT) is a kind of exotoxin caused by Corynebacterium diphtheria, infected by pbacteriophage. DT can combine with sensitive cells immediately and lead to kinds of clinical symptoms, such as cardiomyopathy and adrenopathy, etc. The toxicity of DT is so strong that one or two molecules of DT could destroy one molecule of eucaryote cell, especially effective for tumor cells. Owing to the notable feature of the structure and function, DT becomes the most usually applied bacterial toxin in the research of leading therapeutic medicine. Any combination of some toxins and target—specific carriers become as selective therapeutic medicine especially for special tumor cells in clinical recently and achievements are made in curative effect. Studies on theoretical calculation of DT's active site and structure-activity relationship could afford theoretical basis for modification and clues for new drug development. The structure of DT consists of three domains, catalytic domain (C-domain), transmembrane domain (T-domain) and receptor binding domain (R-domain). The C-domain, consisting of 193 amino acid residues, is the main region of DT, causing toxicity. In order to investigate the structure of active sites, the action mechanism, the structure-activity relationship and afford theoretical basis for modification, four fragments, S~(146)～Q~(155), S~(19)～N~(45), N~(45)～S~(55), T~(56)～N~(71) were cut off from the C-domain and each of them contains only one α-helix according to the crystal structure of DT. Electronic structures of them are calculated by semi-empirical method of quantum chemistry. All of the four fragments contain the main amino acid residues in the active site "cleft" described in references.
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