title: Stereoelectronic factors in the binding of substrate analogues and inhibitors to purine nucleoside phosphorylase isolated from human erythrocytes.
abstract: Several aspects of the stereoelectronic requirements of substrates of human erythrocytic purine nucleoside phosphorylase (E.C. 2.4.2.1) were elucidated providing the following information: (a) the N1 position cannot have a nonhydrogen substituent; (b) the 5'-OH group must be present for catalytic activity to be exhibited but is not an essential functional group for inhibitory action to be observed; (c) on the C8 position groups larger than -NH2 or -Br cannot be accommodated; (d) the syn-glycosyl conformation (i.e., 8-bromoguanosine) is acceptable but may not be an absolute requirement for phosphorolysis; (e) among nucleic base inhibitors methylation at N3, N7, or N9 vastly decreases the inhibitory properties as does a nitrogen in lieu of C-H in the 8 position. The results clearly indicate that this enzyme differs in its stereoelectronic requirements from the Escherichia coli enzyme.
mesh_terms: D001667:Binding, Competitive; D003853:Deoxyribonucleosides / Q000097:blood / Q000378:metabolism; D004912:Erythrocytes / Q000201:enzymology*; D006151:Guanosine / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism; D006157:Guanosine Monophosphate / Q000097:blood / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007288:Inosine / Q000031:analogs & derivatives / Q000097:blood; D007700:Kinetics; D008745:Methylation; D008968:Molecular Conformation; D010430:Pentosyltransferases / Q000097:blood*; D011485:Protein Binding; D011683:Purine-Nucleoside Phosphorylase / Q000097:blood*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D003853:Deoxyribonucleosides; D006151:Guanosine; D007288:Inosine; D006157:Guanosine Monophosphate; D010430:Pentosyltransferases; D011683:Purine-Nucleoside Phosphorylase