Structure analyses of key enzymes from trypanosoma and malaria for the development of new drugs

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Since there is no effective medicine for infectious disease caused by Trypanosoma and malaria, many peoples live in tropical were killed. In order to develop new drugs for these, we focused to metabolic enzymes in Trypanosoma and malalia as target, and studied specific inhibitors.(1) Methionine aminopeptidase from P. falciparum ; We develop new assay method of methionine aminopeptidase using prolyl aminopeptidase. We cloned the enzyme gene and expressed in E. coli. Using the new assay method, specific inhibitor have been screened. A family of structurally related inhibitors containing a 2-(2pyridinyl)- pyrimidine was identified in compound library. Inhibitors were also found in microbial products and plant extract.(2) Oligopeptidase B from trypanosomiasis : The enzyme plays a key role in the pathogenesis of trypanosomiasis. We found protamine act unique and potent inhibitor for oligopeptidase B from trypanosoma. In order to clarify the mechanism of inhibition, we crystallized the enzyme and studied X-ray crystallography. The crystallographic parameters were a=b=123.9, C=248.0 A gamma=120 degree and p hexagonal.(3) Specific inhibitors for aminopeptidase N and prolyl oligopeptidase from them were also studied.