Substrate specificities of 5′-deoxy-5′-methylthioadenosine phosphorylase from Trypanosoma brucei brucei and mammalian cells

• Published in: Molecular and biochemical parasitology Vol. 27; no. 2; pp. 109 - 118
• Main Authors: Ghoda, Lucy Y., Savarese, Todd M., Northup, Catherine H., Parks, Robert E., Garofalo, Joanne, Katz, Libby, Ellenbogen, Barbara B., Bacchi, Cyrus J.
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 15.01.1988; Elsevier Science
• Subjects: 5′-Methylthioadenosine metabolism; 5′-Methylthioadenosine phosphorylase; adenosine; Adenosine - analogs & derivatives; Adenosine - metabolism; Animals; Biochemistry. Physiology. Immunology. Molecular biology; Biological and medical sciences; Deoxyadenosines; Fundamental and applied biological sciences. Psychology; guanosine; Human protozoal diseases; Infectious diseases; inosine; Medical sciences; Mice - metabolism; N-Glycosyl Hydrolases - metabolism; Neoplasm Proteins - metabolism; Parasitic diseases; Pentosyltransferases - metabolism; Protozoa; Protozoal diseases; Purine nucleoside hydrolase; Purine-Nucleoside Phosphorylase - metabolism; purines; Purines - metabolism; Sarcoma 180 - enzymology; Species Specificity; Substrate Specificity; Thionucleosides - metabolism; Tropical medicine; Trypanosoma brucei; Trypanosoma brucei brucei; Trypanosoma brucei brucei - enzymology; Trypanosomiasis; MeSRib-1-P; 5′-Methylthioadenosine metabolism; 5′-Methylthioadenosine phosphorylase; MeSAdo; DFMO; Purine nucleoside hydrolase; Trypanosoma brucei brucei; Ado; Protozoa; Cell culture; Vertebrata; Mammalia; 5'-Methylthioadenosine phosphorylase; Enzyme; Substrate specificity; Rhizoflagellata; Microorganism culture; Pathogen; Trypanosoma brucei
• ISSN: 0166-6851; 1872-9428
• DOI: 10.1016/0166-6851(88)90030-8

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.