Abstract
Hunter syndrome or Mucopolysaccharidosis II is an inherited X linked disease, caused by mutations in iduronate 2 sulfatase (IDS), enzyme which catalyzes the initial step reaction of heparan and dermatan sulfate degradation. Allelic heterogeneity in MPSII challenges genotype-phenotype correlation. With the aim of understanding the repercussion of mutations on enzyme structure-function, we performed protein modeling and docking simulations with wild and mutant forms of hIDS. Mutations were obtained from a molecular study conducted in Colombian patients. Point mutations affected substrate-protein interactions. In the case of S71N (attenuated phenotype) further experimentation is required. Novel mutants P160SfsX4, D190Pfs13X and P185GfsX2 have a severely distorted conformation. Detailed analysis of the ligand-protein interaction is also of great significance in designing molecules for treatment. This is the first report of molecular docking performed with wild and mutant forms of iduronate-2-sulfatase as a bioinformatical approach to phenotype-genotype correlation in patients with Hunter Syndrome in Colombia.
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Galvis, J., González, J., Torrente, D., Velasco, H., Barreto, G.E. (2014). In silico Analysis of Iduronate 2 Sulfatase Mutations in Colombian Patients with Hunter Syndrome (MPSII). In: Castillo, L., Cristancho, M., Isaza, G., Pinzón, A., Rodríguez, J. (eds) Advances in Computational Biology. Advances in Intelligent Systems and Computing, vol 232. Springer, Cham. https://doi.org/10.1007/978-3-319-01568-2_30
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DOI: https://doi.org/10.1007/978-3-319-01568-2_30
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