Isolation and substrate specificity of an adenine nucleoside phosphorylase from adult Schistosoma mansoni

• Adenine nucleoside phosphorylase (ANP, EC none) activity was identified and partially purified from extracts of Schistosoma mansoni.
• ANP is distinct from the parasite purine nucleoside phosphorylase (EC 2.4.2.1) and mammalian 5′-deoxy-5′-methylthioadenosine phosphorylase (EC 2.4.2.28).
• ANP is specific for adenine nucleosides which includes adenosine analogs modified in the aglycone, pentose or both moieties.
• ANP could play a role as a target for chemotherapy of these parasites by the use of subversive substrates that are selectively activated only by this enzyme.

An adenine nucleoside phosphorylase (ANP, EC none) activity was identified and partially purified from extracts of Schistosoma mansoni by chromatofocussing column chromatography and molecular sieving. The enzyme is distinct from purine nucleoside phosphorylase (PNP, EC 2.4.2.1). ANP is specific for adenine nucleosides which includes adenosine analogs modified in the aglycone, pentose or both moieties. (e.g. 2′-deoxyadenosine, 5′-deoxy-5′-methylthioadenosine, 5′-deoxy-5′-iodo-2-fluoroadenosine, etc.) The enzyme is also distinct from the mammalian 5′-deoxy-5′-methylthioadenosine phosphorylase (MTAP, EC 2.4.2.28) in that it is able of the phosphorolysis of 2′-deoxyadenosine while mammalian MTAP cannot. Because of ANP unique substrate specificity, the enzyme could play a role as a target for chemotherapy of these parasites. Cytotoxic analogs may be designed as subversive substrates that are selectively activated only by the schistosomal ANP.

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