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.
引用
收藏
页码：510 / 515
页数：5
相关论文
共 110 条
[11]  
Kurosawa M(2003)Can correct protein models be identified? Protein Sci. 12 1073-1086
[12]  
Ohkubo M(2005)Identification of correct regions in protein models using structural, alignment and consensus information Protein Sci. 15 900-913
[13]  
Watanabe H(2002)Distance-scaled, finite ideal-gas reference state improves structure-derived potentials of mean force for structure selection and stability prediction Protein Sci. 11 2714-2726
[14]  
Iwasaki H(2004)Crystal structures of beta-galactosidase from J. Mol. Biol. 343 1281-1292
[15]  
Sali A(2004). and its complex with galactose J. Mol. Biol. 337 635-645
[16]  
Blundell TL(2007)Prediction and functional analysis of native disorder in proteins from the three kingdoms of life Bioinformatics 23 2337-2338
[17]  
Fiser A(2007)POODLE-S: web application for predicting protein disorder by using physicochemical features and reduced amino acid set of a position specific scoring matrix BMC Bioinformatics 8 78-W464
[18]  
Do RK(2007)Predicting mostly disordered proteins by using structure-unknown protein data Nucleic Acids Res. 35 W60-103
[19]  
Sali A(1999)PrDOS: prediction of disordered protein regions from amino acid sequence Biochim. Biophys. Acta 1455 85-114
[20]  
Söding J(1994)Molecular basis of GM1 gangliosidosis and Morquio disease, type B. Structure-function studies of lysosomal beta-galactosidase and the non-lysosomal beta-galactosidase-like protein Hum. Genet. 93 109-108
12345678910