Pteridine reductase (PTR1) is a homtetrameric enzyme that is involved the reduction of both pterins and folates in kinetoplastid parasites of the genera Leishmania and Trypanosoma. Since PTR1 provides an alternate pathway for folate reduction and thus confers methotrexate resistance, it has been the target of numerous small-molecule drug-development efforts. While each monomer contains an active site and no cooperativity has been observed in substrate binding, to our knowledge, structural studies have yet to establish whether PTR1 functions only as a tetramer. This presentation will describe efforts to determine whether the tetrameric structure is required for PTR1 function by comparing the activity of computationally predicted interface hot-spot point mutants and chemical cross-linking.

Is Leishmania major pteridine reductase (PTR1) a functional monomer?

256th National Meeting (2018)

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