Molecular docking analysis of a dermatan sulfate tetra-saccharide to human alpha-L-iduronidase

Human alpha-L-iduronidase (IDUA) is a 653 amino acid protein involved in the sequential degradation of glycos-amino-glycans (GAG), heparan sulfate (HS), and dermatan sulfate (DS). Some variants in the IDUA gene produce a deficient enzyme that causes un-degraded DS and HS to accumulate in multiple tissues, leading to an organ dysfunction known as muco-poly-saccharidosis type I (MPS I). Molecular and catalytic activity assays of new or rare variants of IDUA do not predict the phenotype that a patient will develop. Therefore, it is of interest to describe the molecular docking analysis, to locate binding regions of DS to IDUA to better understand the effect of a variant on MPS I development. The results presented herein demonstrate the presence of a polar/acidic catalytic site and a basic region in the putative binding site of DS to IDUA. Further, synthetic substrate docking with the enzyme could help in the predictions of the MPS I phenotype.