Ribonucleotide diphosphate reductase RDPR

From their key role in DNA synthesis it is not surprising that the ribonucleotide reductases are ubiquitous in nature. However, three different types of ribonucleotide reductases are now known, each with variations in their cofactor requirements. The most extensively studied and characterized are the ribonucleotide-diphosphate reductases (RDPRs), in particular the enzyme from Escherichia coli. This reductase consists of two nonidentical subunits, proteins B1 and B2, which form an active 1 1 complex where the interface between these subunits forms the active site, and each subunit alone is devoid of catalytic activity (9). Protein B2 (Mr 78,(XK)) is a dimer and contains two atoms of tightly... 

In a study related to the mechanism of inactivation of ribonucleotide diphosphate reductase (RDPR) by 2 -deoxy-2 -substituted nucleotide analogues, it was found that treatment of nucleosides of type 57 (B=Ura, Ade, X=I, Br, Cl, SMe, N3) with tributylstannane and AIBN gave the d4 products 58, whilst with X=F, OMs or OTs, the 3 -deoxysystem 59 was the product. The results pointed to the loss of radicals rather than anions from C-2 during mechanism-based inactivation of RDPR, and the authors suggest some modifications to Stubbe s mechanistic proposals. ... 

Since 1976 a number of 2 -substituted 2 -deoxynucleoside 5 -diphosphates have been shown to be mechanism-based inactivators of the ribonucleotide reductases from a variety of sources (Table I). This work was extended by Stubbe and Kozarich 50, 51), who studied the reaction of several 2 -halo-substituted 2 -deoxynucleoside 5 -diphosphates with RDPR. Incubation of RDPR with CIUDP, 2 -deoxy-2 -fluoroadenosine 5 -diphosphate (FADP), or 2 -deoxy-2 -fluorocytidine 5 -diphosphate (FCDP) resulted in time-dependent enzyme inactivation, concomitant and stoichiometric loss of all substituents from the ribose moiety, increase in the UV-Vis absorbance of the protein near 320 nm, and... 

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