caa a22 4500 467932956 CHVBK 20180406152948.0 cr unu---uuuuu 170328e20061201xx s 000 0 eng 10.1007/s10545-006-0440-7 doi (NATIONALLICENCE)springer-10.1007/s10545-006-0440-7 Effect of Hunter disease (mucopolysaccharidosis type II) mutations on molecular phenotypes of iduronate-2-sulfatase: Enzymatic activity, protein processing and structural analysis [Elektronische Daten] [K. Sukegawa-Hayasaka, Z. Kato, H. Nakamura, S. Tomatsu, T. Fukao, K. Kuwata, T. Orii, N. Kondo] Summary: Mucopolysaccharidosis II (Hunter disease), a lysosomal storage disorder caused by a deficiency of iduronate-2-sulfatase (IDS), has variable clinical phenotypes. Nearly 300 different mutations have been identified in the IDS gene from patients with Hunter disease, but the correlation between the genotype and phenotype has remained unclear. We studied the characteristics of 11 missense mutations, which were detected in the patients or artificially introduced, using stable expression experiments and structural analysis. The mutants found in the attenuated phenotype showed considerable residual activity (0.2-2.4% of the wild-type IDS activity) and those in the severe phenotype had no activity. In immunoblot analysis, both the 73-75 kDa precursor and processed forms were detected in the expression of 'sattenuated' mutants (R48P, A85T and W337R) and the artificial active site mutants (C84S, C84T). The 73-75 kDa initial precursor was detected in the 'severe' mutants (P86L, S333L, S349I, R468Q, R468L). The truncated 68 kDa precursor form was synthesized in the Q531X mutant. The results of immunoblotting indicated rapid degradation and/or insufficiency in processing as a result of structural alteration of the IDS protein. A combination of analyses of genotype and molecular phenotypes, including enzyme activity, protein processing and structural analysis with an engineered reference protein, could provide an avenue to understanding the molecular mechanism of the disease and could give a useful tool for the evaluation of possible therapeutic chemical compounds. SSIEM and Springer, 2006 Sukegawa-Hayasaka K. Department of Pediatrics, Gifu University Graduate School of Medicine, Gifu, Japan aut Kato Z. Department of Pediatrics, Gifu University Graduate School of Medicine, Gifu, Japan aut Nakamura H. Research Center for Structural Biology, Institute for Protein Research, Osaka University, Osaka, Japan aut Tomatsu S. Department of Pediatrics, Gifu University Graduate School of Medicine, Gifu, Japan aut Fukao T. Department of Pediatrics, Gifu University Graduate School of Medicine, Gifu, Japan aut Kuwata K. Division of Prion Research, Center for Emerging Infectious Diseases (CEID), Gifu University, Gifu, Japan aut Orii T. Department of Human Welfare, Faculty of Human Welfare, Chubu Gakuin University, Gifu, Japan aut Kondo N. Department of Pediatrics, Gifu University Graduate School of Medicine, Gifu, Japan aut Journal of Inherited Metabolic Disease Kluwer Academic Publishers 29/6(2006-12-01), 755-761 0141-8955 29:6<755 2006 29 10545 https://doi.org/10.1007/s10545-006-0440-7 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10545-006-0440-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Sukegawa-Hayasaka K. Department of Pediatrics, Gifu University Graduate School of Medicine, Gifu, Japan aut NATIONALLICENCE 700 1- Kato Z. Department of Pediatrics, Gifu University Graduate School of Medicine, Gifu, Japan aut NATIONALLICENCE 700 1- Nakamura H. Research Center for Structural Biology, Institute for Protein Research, Osaka University, Osaka, Japan aut NATIONALLICENCE 700 1- Tomatsu S. Department of Pediatrics, Gifu University Graduate School of Medicine, Gifu, Japan aut NATIONALLICENCE 700 1- Fukao T. Department of Pediatrics, Gifu University Graduate School of Medicine, Gifu, Japan aut NATIONALLICENCE 700 1- Kuwata K. Division of Prion Research, Center for Emerging Infectious Diseases (CEID), Gifu University, Gifu, Japan aut NATIONALLICENCE 700 1- Orii T. Department of Human Welfare, Faculty of Human Welfare, Chubu Gakuin University, Gifu, Japan aut NATIONALLICENCE 700 1- Kondo N. Department of Pediatrics, Gifu University Graduate School of Medicine, Gifu, Japan aut NATIONALLICENCE 773 0- Journal of Inherited Metabolic Disease Kluwer Academic Publishers 29/6(2006-12-01), 755-761 0141-8955 29:6<755 2006 29 10545 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer