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Title

 

 

 

 

 

A docking model of human ribonucleotide reductase with flavin and phenosafranine

Authors

 

Panneerselvam Lakshmi Priya, Piramanayagam Shanmughavel*

Affiliation

 

Computational Biology and Bioinformatics Laboratory, Department of Bioinformatics, Bharathiar University, Coimbatore 641 046, India

 

Email

 

 shanvel_99@yahoo.com

Article Type

 

Hypothesis

Date

 

Received May 10, 2009; Revised June 05, 2009; Accepted June 13, 2009; Published September 30, 2009

Abstract

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 growth has made this an important target for anticancer therapy. Increased RNR activity has been associated with malignant transformation and tumor cell growth. In recent years, several RNR inhibitors, including Triapine, Gemcitabine and GTI-2040, have entered the clinical trials. Our current work focuses on an attempted to dock this inhibitors Flavin and Phenosafranine to curtail the action of human RNR2. The docked inhibitor Flavin and Phenosafranine binds at the active site with THR176, which are essential for free radical formation. The inhibitor must be a radical scavenger to destroy the tyrosyl radical or iron metal scavenger. The iron or radical site of R2 protein can react with one-electron reductants, whereby the tyrosyl radical is converted to a normal tyrosine residue. However, compounds such as Flavin and Phenosafranine were used in most of the cases to reduce the radical activity. The docking study was performed for the crystal structure of human RNR with the radical scavengers Flavin and Phenosafranine to inhibit the human RNR2. This helps to understand the functional aspects and also aids in the development of novel inhibitors for the human RNR2.

 

Keywords

 Ribonucleotide reductase, Flavin, Phenosafranine, radical scavenger, inhibitors

 

Citation

 

Priya & Shanmugavel, Bioinformation 4(3): 123-126 (2009)

Edited by

 

P. Kangueane

 

ISSN

 

0973-2063

 

Publisher

 

Biomedical Informatics

License

 

 

This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.