Structural analysis of misfolding equilibrative nucleoside transporter 3in H-syndrome

Abstract

Recent findings interpret that misfolding, aggregation and accumulation of proteins consequence in some disease. Evidence from different practices intensely support this hypothesis and demonstrate that a common therapy for these pernicious disorders might be possible. However, H syndrome is related to the recessive mutations in SLC29A3, encoding the equilibrative nucleoside transporter Equilibrative nucleoside transporter 3 (hENT3) which is expressed in mitochondria. The aim of this study is to investigate the misfolding and aggregation of ENT3 protein regarding in H syndrome, which can be a potential target for therapeutic interference in this disorder. Therefore, the 3D structure of the ENT3 protein was assumed using the I-TASSER online server and the best-predicted structure with the maximum confidence score (C-Score) was selected. The reliability and quality of the structure were evaluated by Z-score. However, the structural model of the selected mutant was accomplished using the I-TASSER server. The comparison with the corresponding of non-mutated structure and structural difference between mutant and wild-type structures was demonstrated by PyMOL.In the present study, computational models combined with experimental approaches provide new insights into the ENT3 which could lead to expanding new classes of nucleobase analogs for treatment and quintessential therapeutic strategies for H syndrome and some other diseases like cancer and viral infection.