Stereoelectronic factors in the binding of substrate analogues and inhibitors to purine nucleoside phosphorylase isolated from human erythrocytes.

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.