Explain the Structure of Type I RNR
Ribonucleotide reductase (RNR) is an essential enzyme responsible for reducing ribonucleotides into deoxyribonucleotides, which are the building blocks of DNA. Type I RNR is the most studied form and is found in many organisms, including bacteria and eukaryotes.
Subunit Composition
- Large Subunit (R1 or α-subunit):
- Contains the catalytic site where the reduction reaction takes place
- Has two allosteric sites: specificity site and activity site
- Small Subunit (R2 or β-subunit):
- Contains a diiron center and a stable tyrosyl radical needed to initiate catalysis
- Transfers the radical to the catalytic subunit via long-range electron transfer
Functional Domains
- Catalytic Site: Converts ribonucleotides (NDPs) to deoxyribonucleotides (dNDPs)
- Allosteric Sites:
- Activity site: Regulates overall enzyme activity (ATP activates, dATP inhibits)
- Specificity site: Determines which ribonucleotide is reduced, maintaining balanced dNTP pools
Mechanism of Action
Type I RNR operates via a radical-based mechanism. The β-subunit generates a tyrosyl radical, which travels through a conserved pathway to the α-subunit to initiate the reduction of the ribonucleotide substrate.
Biological Importance
- Crucial for DNA synthesis and repair
- Highly regulated to prevent imbalanced dNTP pools, which can be mutagenic
Type I RNR is a key target for cancer and antiviral drugs due to its pivotal role in DNA precursor synthesis.