Structure of a ribonucleotide reductase R2 protein radical

Science. 2023 Oct 6;382(6666):109-113. doi: 10.1126/science.adh8160. Epub 2023 Oct 5.

Abstract

Aerobic ribonucleotide reductases (RNRs) initiate synthesis of DNA building blocks by generating a free radical within the R2 subunit; the radical is subsequently shuttled to the catalytic R1 subunit through proton-coupled electron transfer (PCET). We present a high-resolution room temperature structure of the class Ie R2 protein radical captured by x-ray free electron laser serial femtosecond crystallography. The structure reveals conformational reorganization to shield the radical and connect it to the translocation path, with structural changes propagating to the surface where the protein interacts with the catalytic R1 subunit. Restructuring of the hydrogen bond network, including a notably short O-O interaction of 2.41 angstroms, likely tunes and gates the radical during PCET. These structural results help explain radical handling and mobilization in RNR and have general implications for radical transfer in proteins.

MeSH terms

  • Bacterial Proteins* / chemistry
  • Catalytic Domain
  • Crystallography, X-Ray / methods
  • Electron Transport
  • Entomoplasmataceae* / enzymology
  • Protons
  • Ribonucleotide Reductases* / chemistry

Substances

  • Protons
  • Ribonucleotide Reductases
  • anaerobic ribonucleotide reductase
  • Bacterial Proteins

Supplementary concepts

  • Mesoplasma florum