-!- This enzyme is responsible for the de novo conversion of ribonucleoside diphosphates into deoxyribonucleoside diphosphates, which are essential for DNA synthesis and repair. -!- There are three types of this enzyme differing in their cofactors. -!- Class Ia enzymes contain a diferric-tyrosyl radical, class Ib enzymes contain a dimanganese-tyrosyl radical, and class II enzymes contain adenosylcobalamin. -!- In all cases the cofactors are involved in generation of a transient thiyl radical on a cysteine residue, which attacks the substrate, forming a ribonucleotide 3'-radical, followed by water loss to form a ketyl radical. -!- The ketyl radical is reduced to 3'-keto-deoxynucleotide concomitant with formation of a disulfide anion radical between two cysteine residues. -!- A proton-coupled electron-transfer from the disulfide radical to the substrate generates a 3'-deoxynucleotide radical, and the the final product is formed when the hydrogen atom that was initially removed from the 3'-position of the nucleotide by the thiyl radical is returned to the same position. -!- The disulfide bridge is reduced by the action of thioredoxin. -!- Cf. EC 1.1.98.6 and EC 1.17.4.2.