Figure 1. Structure and regulation of ribonucleotide reductase.

(A) Reaction of class Ia RNR. (B) Diagram of allosteric regulation of activity and substrate specificity by ATP and deoxyribonucleoside triphosphate (dNTP) effectors. The blue box represents RNR catalyzing NDP reduction (black arrows). Downstream black arrows indicate further processing by other enzymes to dNTPs. The dNTP products of the pathway feed back to alter the preference of RNR toward the indicated substrate (dashed grey lines) and promote or inhibit overall activity (green and red dashed lines, respectively). (C) Schematics of human α and β subunits highlighting major structural features. Unstructured N- and C-termini are indicated by dashed lines. (D) Structures of the human α and β homodimers. Subunits of α₂ (from our α₆ cryo-EM structure) are colored as in panel C with one subunit in faded colors. Bound CDP substrate (orange) and dATP effectors (yellow) are shown as spheres. Subunits of β₂ (PDB: 2UW2) are orange and red, iron atoms in green. Dashed lines indicate unstructured termini.