Department of Crystallography and Biophysics, University of Madras
○Sampath Natarajan Ponnuswamy Mondikalipudur Nanjappa

Ribonucleotide reductase(RNR) is a ubiquitous cytosolic enzyme, responsible for converting ribonucleotides into deoxyribonucleotides, the eventual substrates for DNA polymerase and also repairs DNA in all living cells. Thus cell division makes it a potential target for designing drug to inhibit cell growth in cancer therapy. This cell division is performed with the help of free radicals, which is from tyrosine residue. An increased interest in RNR as a target for cancer therapy is seen ever since the human RNR is regulated by p53 enzyme. The p53 enzyme actively suppresses the tumor formation but on mutation it leads to several forms of cancer. As much as over 80% of the human tumors have been found to contain mutations in p53 enzyme and the cancer cells would die if the normal RNR were inhibited. This appears to be a good strategy but unfortunately the picture seems to be more complicated. A new strategy to kill the cancer cells would be a specific inhibitor, which inhibits the RNR-R2 enzyme which is crucial to cancer cells after DNA damage since they cannot induce the p53R2 due to lack of p53. Therefore an understanding of the molecular mechanism of RNR is essential for the design of new cytostatic drugs. The inhibitor must be a radical scavenger to destroy the tyrosyl radical or iron metal scavenger (which affects the iron center). In this view the modeling studies on human RNR-R2 were made to understanding the interaction with radical scavengers through the docking studies. Further more, the radical mechanism of action of inhibitors will be proposed. In addition to this how the metal scavenger drugs are better than radical scavenger drugs to curtail action of RNR enzyme will be discussed in details.