An Approach to Increase the Efficiency of Uricase by Computational Mutagenesis

Uricase is widely used to treat hyperuricemia and gout. Its clinical use is complicated by patients severe allergy, hypersensitivity and anaphylactic reactions. Uricase from Arthrobacter globiformis (Ag) and Bacillus fastidious (Bf) was chosen to improve enzyme binding energy by reducing the deleterious effects in treatment. Reducing the adverse effects of uricase was achieved by in silico mutagenesis. Pymol altered the active site amino acids of uricase from both sources.The ligand uric acid was docked to mutated uricase by Autodock 4.0, which helps in improving uricase binding energy. It has been found that mutation of Val64 with Alanine in Ag uricase and Gly42 with Isoleucine in Bf uricase improved the binding energy ability of enzyme by 50%. The binding affinity of Ag uricase docked with uric acid was found to be -8.414 Kcal/mole while for the mutated protein it was found to be -8.570 Kcal/mole. Binding energies for Bf uricase were found to be -5.221, and 5.389 Kcal/mole for native and mutated protein. We infer that our In silico model with improved uricase binding energy can assist to make a potent drug by the help of protein mutagenesis which leads to develop a drug with minimum adverse effects to treat hyperuricemia.