A docking model of human ribonucleotide reductase with flavin and phenosafranine

Ribonucleotide Reductase (RNR) is an enzyme responsible for the reduction of ribonucleotides to their corresponding Deoxyribonucleotides(DNA), which is a building block for DNA replication and repair mechanisms. The key role of RNR in DNA synthesis and control in cell growthhas made this an important target for anticancer therapy. Increased RNR activity has been associated with malignant transformation and tumorcell growth. In recent years, several RNR inhibitors, including Triapine, Gemcitabine and GTI-2040, have entered the clinical trials. Our currentwork focuses on an attempted to dock this inhibitors Flavin and Phenosafranine to curtail the action of human RNR2. The docked inhibitor Flavinand Phenosafranine binds at the active site with THR176, which are essential for free radical formation. The inhibitor must be a radical scavengerto destroy the tyrosyl radical or iron metal scavenger. The iron or radical site of R2 protein can react with one-electron reductants, whereby thetyrosyl radical is converted to a normal tyrosine residue. However, compounds such as Flavin and Phenosafranine were used in most of the casesto reduce the radical activity. The docking study was performed for the crystal structure of human RNR with the radical scavengers Flavin andPhenosafranine to inhibit the human RNR2. This helps to understand the functional aspects and also aids in the development of novel inhibitorsfor the human RNR2.