Homology Modeling of Turmerin and its Molecular Interaction with Human Erythropoietin

Abstract

Erythropoietin, a protein, is a potent ischemia-induced angiogenic factor that acts independently of VEGF during retinal angiogenesis in proliferative diabetic retinopathy. Turmerin, a protein of Curcuma longa L. Inspite of many other medicinal properties possesses antidiabetic properties too. The molecular interactions of erythropoietin and turmerin were studied for exploring the protein-protein interaction against diabetic retinopathy. Methods: In attempts for identification of the binding sites of turmerin, homology modeling was performed. The protein sequence of turmerin was obtained from GenBank. The atomic coordinates was retrieved from Protein Data Bank. Molecular structures of turmerin were modeled by using restraint-based modeling implemented in the program Modeller 9.9. Several models were generated. The quality and stereochemistry of the models were evaluated using the program Procheck. Turmerin model was docked to human erythropoietin using Hex 4.5. Docking studies were conducted to obtain modeled structures of the turmerin-erythropoietin complex. Results: The key amino acid residues within the docking complex model involved in the interaction between Turmerin (t) and human erythropoietin (e) were tVal10, tLeu11, tSer28, tThr54, tGly66, tPro 77 and ePro7, eCys39, eVal98, eLeu129, eThr146, eMet198, eSer211. The docking result indicated that the complex could be stabilized by hydrogen bonding. Conclusion: Our findings provide a detailed prediction of key residues that interact at the turmerin-erythropoietin proteinprotein interface. The predicted interaction complex is helpful in understanding structural insights, and may lead to the establishments of prophylactic and therapeutic approaches for the same in diabetic retinopathy.