STRUCTURE-FUNCTION RELATIONSHIP OF TRICHOSANTHIN

Trichosanthin(TCS), a 27 kDa ribosome inactivating protein extracted f rom the root tuber of 'Trichosanthes plant, was subjected to limited c hymotrypsin digestion and three peptide fragments designated TCS-F1 72 -247, TCS-F2 100-247, and TCS-F3 133-247 Were generated. The RNA-N-gly cosidase and cytotoxic activities of the TCS fragments were compared w ith that of inact TCS. TCS-F1 and TCS-F2 were biologically active, whi le TCS-F3 was completely inactive. Dose-dependent studies showed that TCS-F1 and TCS-F2 were less potent in their trophoblast cytotoxicity t han intact TCS, however, full biological effect could still be obtaine d with a higher dosage. Based on the known three-dimensional structure of TCS, we postulate that the putative active site of TCS is located at amino acid residues 110 to 174.