Dihydrofolate Reductases: Structural and Mechanistic Aspects *

In cancer chemotherapy the advent of each clinically useful agent has been followed by a search for the molecular receptor or “target” for that drug. In the case of the folate antagonists such as aminopterin or amethopterin (Methotrexate) , which have been used extensively in the treatment of leukemia, lymphoma, and choriocarcinoma,’ the target is presumed to be dihydrofolate reductase, an enzyme whose primary function is catalysis of reaction ( 1 ) , the structural details of which are presented in FIGURE 1.

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