Ribonucleotide reductases cobalt

Thiobacillus ferrooxidans function. 6, 651 Rhus vernicifera stellacyanin structure, 6,651 Riboflavin 5 -phosphate zinc complexes, 5,958 Ribonucleotide reductases cobalt, 6,642 iron, 6,634... 

Tkiobacillus ferrooxidans function, 651 Rhus vernicifera siellacyanin structure, 651 Ribonucleotide reductases cobalt, 642 iron, 634... 

The next five transition metals iron, cobalt, nickel, copper and zinc are of undisputed importance in the living world, as we know it. The multiple roles that iron can play will be presented in more detail later in Chapter 13, but we can already point out that, with very few exceptions, iron is essential for almost all living organisms, most probably because of its role in forming the amino acid radicals required for the conversion of ribonucleotides to deoxyribonucleotides in the Fe-dependent ribonucleotide reductases. In those organisms, such as Lactobacilli6, which do not have access to iron, their ribonucleotide reductases use a cobalt-based cofactor, related to vitamin B12. Cobalt is also used in a number of other enzymes, some of which catalyse complex isomerization reactions. Like cobalt, nickel appears to be much more extensively utilized by anaerobic bacteria, in reactions involving chemicals such as CH4, CO and H2, the metabolism of which was important... 

A second group of ribonucleotide reductases (Class II), found in many bacteria, depend upon the cobalt-containing vitamin B12 coenzyme which is discussed in Section B. These enzymes are monomeric or homodimeric proteins of about the size of the larger a subunits of the Class I enzymes. The radical generating center is the 5 -deoxyadenosyl coenzyme.350 364 365... 

Reduction of ribonucleotides to deoxyribonucleotides, the essential first step in the synthesis of DNA, is catalyzed by the enzyme ribonucleotide reductase (equation 25). Three different types of ribonucleotide reductase are known, which differ in their requirement for metal, namely cobalt... 

Among the first enzymes studied by EPR were ethanolamine deaminase and AdoCbl-dependent ribonucleotide reductase (Babior et al., 1974 Orme-Johnson et ah, 1974). The EPR spectrum of ethanolamine deaminase was extensively characterized in the presence of 2-aminopropanol, which is a slow substrate for the enzyme. It exhibits a broad feature at g = 2.34 attributed to Cbl(II), and a sharp doublet at g = 2.01 attributed to an organic radical. Using isotopically-labeled substrates, the organic radical was identified as the C-1 radical of 2-aminopropanol (Babior et al., 1974). The doublet splitting was attributed to dipolar coupling of the Co(II) spin with the substrate radical and the distance between cobalt and the substrate radical was calculated to be about 6. Thus, these experiments yielded the first structural information on the active site of a Bn enzyme. 

Brown, M. L., and Li, J., 1998, Activation parameters for the carbon-cobalt bond homolysis of coenzyme B12 induced by the B[2-dependent ribonucleotide reductase from Lactobacillus leichmannii. J. Am. Chem. Soc. 120 9466n9474. 

Licht, S. S., Lawrence, C. C., and Stubbe, J., 1999, Class II ribonucleotide reductases catalyze carbon-cobalt bond reformation on every turnover. J. Amer. Chem. Soc. 121 7463n7468. 

The participation of a cysteine thiol in the abstraction of hydrogen from ribose C-3 coenzyme B12, which is not a feature of any other of the reactions of Table 1, leads to exchange of H between this thiol group, the 5 -methylene group of coenzyme Bi2 and water (22). It was also shown that ribonucleotide reductase catalyzes the conversion of adenosylcobalamin labeled with one deuterium atom at C-5 (initial R/S ratio = 3 1) to monodeuterated coenzyme with R/S ratio = 1. This result shows that the cobalt-carbon 0-bond is reversibly cleaved to a 5 -deoxyadenosyl radical, which permits rotation about the C-47C-5 0-bond. 

The other type of radical chemistry of importance in the carbohydrate field is one-electron reductions. A handful of these reactions (such as the metallic Zn reduction of acetobromoglucose to triacetylglucal) have been used in synthesis for decades, but, starting with the Barton-McCombie deoxygenation of sugars in the mid-1970s there has been an explosion of interest, as increasingly sophisticated cascades of elementary radical steps have been devised. Such reactions are driven by the homolysis of weak bonds such as Sn-H or N-O under conditions of photolysis or mild thermolysis. Nature uses a similar basic principle in Type II ribonucleotide reductases, where the weak bond in question is the cobalt-carbon a bond in the corrin cofactor. ... 

Ribonucleotide reductase presents an exception to the above mechanism where the working radical is a thiyl derived from an active-site cysteine (C408 in the Lactobacillus Idchmannii enzyme) rather than dAdo [35], Mutation of C408 leads to failure of the mutant enzyme to generate detectable levels of cob(ii)alamin. However, the mutant catalyzes epimerization of AdoCbl that is stereoselectively deuter-ated at the 5 carbon bonded to cobalt [36], This indicates that transient cleavage of the cobalt-carbon bond occurs, but when radical propagation to C408 is precluded, recombination of dAdo and cob(ii)alamin is favored. 

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