Homology modeling and virtual screening of ubiquitin conjugation enzyme E2A for designing a novel selective antagonist against cancer

Abstract

Cancer is a major health problem in the world. The initiation and progression of cancer is due to imbalance between the programmed cell growth and death. These processes are triggered by the ubiquitin family enzymes. The ubiquitin-like proteins are responsible for the cell metabolism. Ubiquitin-dependent proteolysis by the 26s proteasome plays a crucial role in cell cycle progression as well as in tumorigenesis. In the ubiquitin proteasomal degradation pathway, ubiquitin conjugation enzyme E2A (UBE2A) binds with ubiquitin ligase RAD18, results in polyubiquitation reaction and cell cycle progression. UBE2A is an important contributing factor for the control of tumorigenesis. In the present work, the 3D model of the protein UBE2A was generated by homology modeling technique. The generated 3D structure of the UBE2A was validated, and active site was identified using standard computational protocols. The active site was subjected to structure-based virtual screening using small molecule data banks, and new molecules were identified. The ADME properties of the new ligand molecules were predicted, and the new ligands are identified as potent UBE2A antagonists for cancer therapy.

• ADME
• cancer therapy
• RAD18
• tumorigenesis
• ubiquitin ligase

Acknowledgements

The authors VR, RKD and RV acknowledge the Principal and Head Department of Chemistry, University College Science, Osmania University, Hyderabad, India, for providing facilities to carry out this work.

Declaration of interest

The author VR acknowledges Council of Scientific and Industrial Research, India, for the financial support (File No: 09/132(0821)/2012-EMR-I). The authors have no conflict of interest.

Supplementary material available online

Supplementary Figure 1.