Document Type : Regular Article
Department of Chemical Engineering, NITK Surathkal, Mangalore, India
Uricase is a therapeutic enzyme that has application in adjuvant chemotherapy and management of treatment-resistance hyperuricemia. It constitutes a key element in gout treatment, a type of arthritis affecting humans due to increased serum uric acid levels. Available two formulations of uricase from the bacterial source are characterized by their high immunogenicity, resulting in the drug's inactivation and hypersensitivity reactions in many patients. Identifying and modifying epitopic areas of uricase from Aspergillus flavus and Candida utilis by in silico approach to lower protein immunogenicity. Both Uricase B-cell epitopes were predicted using Emini surface accessibility and Parker hydrophilicity. Mutations were made to the hot-spot residues to diminish the epitope's antigenicity. Finally, molecular docking was used to examine the effect of mutagenesis on uricase catalytic activity and structural stability. We performed the prediction of immunogenic and allergenic epitopes in the structure of uricase by using the relative frequency of immunogenic peptides. This study showed no signiﬁcant diﬀerences in the level of immunogenicity between both enzymes. However, from a structural point of view, in our knowledge, this is the ﬁrst research describing the structural antigenic determinants that contribute to the hypersensitivity response to this treatment.