Substrate specificities of 5'-deoxy-5'-methylthioadenosine phosphorylase from Trypanosoma brucei brucei and mammalian cells.
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.
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*
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