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  • Title: Protein properties of the subunits of ribonucleotide reductase and the specificity of the allosteric site(s).
    Author: Cory JG, Sato A, Brown NC.
    Journal: Adv Enzyme Regul; 1986; 25():3-19. PubMed ID: 3544706.
    Abstract:
    Ribonucleotide reductase catalyzes the critical reaction in which the deoxyribonucleotides required for DNA replication are synthesized de novo. This enzyme consists of two non-identical protein subunits, both of which are required for enzymatic activity. These subunits consist of a non-heme iron and an effector-binding subunit. These subunits are not coordinately regulated as the cells pass from G1 to the S phase of the cell cycle. Studies carried out with the holoenzyme and the isolated subunits indicate that the effector-binding subunit is more susceptible to chymotrypsin and the sulfhydryl reagents, pCMB and NEM, than is the non-heme iron subunit. The non-heme iron subunit is more susceptible to trypsin than is the effector-binding subunit. The presence of ATP or dATP protects the effector-binding subunit from proteolysis by either trypsin or chymotrypsin. The loss of activity in the holoenzyme, as a result of proteolysis, parallels the loss of the particular subunit. These results demonstrate that the protein properties of the subunits are significantly different to account for the differential turnover. The binding of nucleotides to the effector-binding site(s), which in turn regulates ribonucleotide reductase activity, is very specific. Formycin 5'-triphosphate and etheno-ATP could not replace ATP in the CDP reductase reaction. 2',3'-DideoxyATP was 5-fold less active than dATP as a negative effector; etheno-dATP was not inhibitory. AraGTP and BuPdGTP could not replace dGTP as a positive effector of ADP reduction. BuPdGTP, but not araGTP, served as an inhibitor of CDP reduction. 2',3'-DideoxyTTP was much less active as either an activator of GDP reduction or an inhibitor of ADP reduction. These studies indicate that the binding to the allosteric sites is highly specific and suggest that the structural requirements for the binding of activators are different from the structural requirements for the binding of inhibitors.
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