Structural bases of GM1 gangliosidosis and Morquio B disease

被引:0
作者
Mizuki Morita
Seiji Saito
Kazuyoshi Ikeda
Kazuki Ohno
Kanako Sugawara
Toshihiro Suzuki
Tadayasu Togawa
Hitoshi Sakuraba
机构
[1] Agricultural Bioinformatics Research Unit,Department of Biotechnology
[2] Graduate School of Agricultural and Life Sciences,Department of Clinical Genetics
[3] The University of Tokyo,Department of Analytical Biochemistry
[4] Graduate School of Agricultural and Life Sciences,undefined
[5] The University of Tokyo,undefined
[6] NPO for the Promotion of Research on Intellectual Property Tokyo,undefined
[7] Meiji Pharmaceutical University,undefined
[8] Meiji Pharmaceutical University,undefined
[9] 7Current address: Pharma Design,undefined
[10] 2-19-8,undefined
[11] Hatchobori,undefined
[12] Chuo-ku,undefined
[13] Tokyo 104-0032,undefined
[14] Japan.,undefined
[15] 8Current address: Astellas Pharma,undefined
[16] 21 Miyukigaoka,undefined
[17] Tsukuba,undefined
[18] Ibaraki 305-8585,undefined
[19] Japan.,undefined
来源
Journal of Human Genetics | 2009年 / 54卷
关键词
β-galactosidase; GM1 gangliosidosis; Morquio B disease; protein structure;
D O I
暂无
中图分类号
学科分类号
摘要
Allelic mutations of the lysosomal β-galactosidase gene cause heterogeneous clinical phenotypes, such as GM1 gangliosidosis and Morquio B disease, the former being further classified into three variants, namely infantile, juvenile and adult forms; and heterogeneous biochemical phenotypes were shown in these forms. We tried to elucidate the bases of these diseases from a structural viewpoint. We first constructed a three-dimensional structural model of human β-galactosidase by means of homology modeling. The human β-galactosidase consists of three domains, such as, a TIM barrel fold domain, which functions as a catalytic domain, and two galactose-binding domain-like fold domains. We then constructed structural models of representative mutant β-galactosidase proteins (G123R, R201C, I51T and Y83H) and predicted the structural change associated with each phenotype by calculating the number of affected atoms, determining the root-mean-square deviation and the solvent-accessible surface area, and by color imaging. The results show that there is a good correlation between the structural changes caused by amino-acid substitutions in the β-galactosidase molecule, as well as biochemical and clinical phenotypes in these representative cases. Protein structural study is useful for elucidating the bases of these diseases.
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页码:510 / 515
页数:5
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