The evolution of ribonucleotide reduction revisited

Area of Science:

• Biochemistry
• Molecular Biology
• Evolutionary Biology

Background:

• Ribonucleotide reductases (RNRs) are essential enzymes responsible for synthesizing deoxynucleotides, the building blocks of DNA.
• These enzymes are crucial for DNA replication and repair processes in all known organisms.
• RNRs are classified into three distinct groups based on their unique metallo-cofactor requirements.

Purpose of the Study:

• To explore the evolutionary divergence of Ribonucleotide reductases (RNRs).
• To highlight the role of chemistry in the evolution of RNR enzyme classes.
• To understand the structural and mechanistic commonalities among different RNR classes.

Main Methods:

• Comparative analysis of RNR structures across different classes.
• Investigation of the free radical chemistry employed by RNRs.
• Phylogenetic analysis to infer evolutionary relationships.

Main Results:

• All RNR classes utilize sophisticated free radical chemistry for nucleotide reduction.
• Significant structural similarities exist in the active sites of RNR subunits across all classes.
• These shared chemical and structural features suggest a common evolutionary origin.

Conclusions:

• The evolution of RNRs from a common progenitor is strongly supported by conserved chemical mechanisms and structural motifs.
• Understanding RNRs provides insights into fundamental biological processes like DNA synthesis and repair.
• The study underscores the critical role of chemistry in shaping enzyme evolution.