Ribonucleotide Reductase: Difference between revisions

The conversion from ribonucleotides to deoxyribonucleotides is a radically-based reaction. Organic free radicals are stored by RNR until they are needed for catalysis. Class I ribonucleotide reductase produces the stable radical, tyrosyl, through the dinuclear iron center of the subunit. This class is the most studied and most well known enzyme that is a part of the RNR family. It is composed of two subunits, alpha and beta, that are homodimeric. The alpha subunit contains the active site and two allosteric sites. The active site contains a catalytic subunit, and the allosteric sites are used for regulation, enzyme activity, and substrate specificity. The beta portion contains the metal cofactor that initiates reduction. Class I is subdivided into three more enzymes that are class Ia, Ib, and Ic. Class one is split even further because it is depending on the specific type of metal center that is needed for protein radical. All three classes share the same function for the beta subunit which is synthesizing the radical which is transferred using a radical transfer pathway. Class Ia requires a di-iron center as the nrdAB gene codes for this enzyme. Class Ib uses either a di-manganese center or a di-ferric center. This specific class differs from the other class I enzymes by lacking the active site located at the N-terminal portion of the protein. This enzyme is coded by the gene nrdHIEF Class Ic is encoded by the nrdAB gene, and it requires a manganese-iron center. Class I and its subdivision are all aerobic and require oxygen for the generation of the radical. This enzyme can be found in eukaryotes, archaea, eubacteria, and bacteriophages. Class II enzymes differ in which it uses cobalamin as a cofactor for the radical. It is encoded by the nrdj gene that harbors the allosteric sites and active site of the enzyme, so the enzyme itself only contains one subunit which is alpha or alpha2.  There is an allosteric specificity site, but no allosteric active site. S-adenosylcobalamin is used as a cofactor in order to generate the cysteinyl radical. <ref name="intro">DOI:10.3389/fcimb.2014.00052</ref> The radical is formed when the bond between the adenosyl and cobalamin is cleaved. It has been recently discovered that several class II RNRs with catalytic domains of the B12-dependent enzyme are related to class I and III RNRs. The reaction for class II can be aerobic or anaerobic because it is oxygen independent. This class is found in archaea, eubacteria, and bacteriophages. It is most studied in microorganisms such as Lactobacillus leichmannii. This class is composed of two proteins that are homodimeric. It is encoded by nrdG and nrdD genes which contain a large catalytic subunit with an active site and two allosteric sites used for regulation. The NrdG protein, activase, initiates the generation of the radical which requires binding of the iron-sulfur cluster in the center of the protein with S-adenosylmethionine. The interaction between the metal center and adenosylmethionine synthesizes a glycyl radical which causes this reaction to be completely anaerobic. The glycyl radical forms at the C-terminal of the protein which is sensitive to oxygen. Along with that and the potential of the metal center oxidizing, this reaction cannot run in the presence of oxygen. This class is found in bacteriophages, eubacteria, and archaea.