title: Substrate specificities of 5'-deoxy-5'-methylthioadenosine phosphorylase from Trypanosoma brucei brucei and mammalian cells.
abstract: The separation by chromatofocusing of two distinct purine nucleoside cleaving activities from crude extracts of Trypanosoma brucei brucei is described. One catalyzes the reversible phosphorolysis of 5'-deoxy-5'-methylthioadenosine (MeSAdo) and adenosine (Ado) and was designated an MeSAdo/Ado phosphorylase, while the other catalyzes the hydrolysis of adenosine, inosine, and guanosine but not MeSAdo. The substrate specificity of trypanosomal MeSAdo/Ado phosphorylase differed from that of a mammalian MeSAdo phosphorylase (derived from murine Sarcoma 180 cells) in that it was able to phosphorolyze 2'-deoxyadenosine, 3'-deoxyadenosine and 2',3'-dideoxyadenosine. In addition, the trypanosomal phosphorylase was able to utilize the nucleoside analog, 6-methylpurine 2'-deoxyribonucleoside, as an alternative substrate, whereas the mammalian enzyme could not. Because of these differences, cytotoxic analogs of MeSAdo may be designed that are selectively activated by the trypanosomal MeSAdo/Ado phosphorylase.
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D003839:Deoxyadenosines; D051379:Mice / Q000378:metabolism*; D009699:N-Glycosyl Hydrolases / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D010430:Pentosyltransferases / Q000378:metabolism*; D011683:Purine-Nucleoside Phosphorylase / Q000378:metabolism*; D011687:Purines / Q000378:metabolism; D012510:Sarcoma 180 / Q000201:enzymology; D013045:Species Specificity; D013379:Substrate Specificity; D013872:Thionucleosides / Q000378:metabolism; D014346:Trypanosoma brucei brucei / Q000201:enzymology*
chemical_list: D003839:Deoxyadenosines; D009363:Neoplasm Proteins; D011687:Purines; D013872:Thionucleosides; C008500:5'-methylthioadenosine; D010430:Pentosyltransferases; D011683:Purine-Nucleoside Phosphorylase; C021784:5'-methylthioadenosine phosphorylase; D009699:N-Glycosyl Hydrolases; C030681:purine nucleosidase; D000241:Adenosine