Structural and immunocytochemical studies on α-N-acetylgalactosaminidase deficiency (Schindler/Kanzaki disease)

Sakuraba, Hitoshi; Matsuzawa, Fumiko; Aikawa, Sei-ichi; Doi, Hirofumi; Kotani, Masaharu; Nakada, Hiroshi; Fukushige, Tomoko; Kanzaki, Tamotsu

doi:10.1007/s10038-003-0098-z

Cited by 44 publications

(27 citation statements)

References 28 publications

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“…The root-mean-square gradient value was set at 0.05 kcal/mol Å . Each mutant model was then superimposed on the wild-type GLA structure based on Ca atoms by the least-square-mean fitting method (Kabsch 1976(Kabsch , 1978Sakuraba et al 2000Sakuraba et al , 2004. In this study, we defined that the structure was affected by an amino acid substitution when the position of an atom in a mutant differed from that in the wild type by more than the cutoff distance (0.15 Å ) based on total RMSD, as described previously (Matsuzawa et al 2005).…”

Section: Amino Acid Substitutions Causing Classic and Variant Fabry Dmentioning

confidence: 99%

Structural characterization of mutant α-galactosidases causing Fabry disease

et al. 2008

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Fabry disease is an inborn error of glycolipid catabolism resulting from lesions in the gene encoding agalactosidase (GLA). To elucidate the basis of Fabry disease, we constructed structural models of mutant GLAs responsible for the disease and calculated indexes, i.e., the numbers of atoms affected in the main chain and side chain of each mutant GLA, the root-mean-square distance values, and the solvent-accessible surface-area values, based on 212 Fabry amino acid substitutions previously reported (196 classic and 16 variant). As two therapeutic options, enzyme replacement and enzyme enhancement, are now available for this disease, proper prediction of the natural outcome and therapeutic efficiency based on the molecular evidence for individual cases are critical for patients' quality of life. Our results revealed that structural changes in the classic Fabry group were generally large and tended to be in the core region of a protein or located in the functionally important region, including the active-site pocket. On the other hand, structural changes in the variant Fabry group were small or localized on the surface of the molecule far away from the active site. We focused on structural changes due to amino acid substitutions for which substrate analogues are effective for improving the stability or transportation of mutant GLAs, and the results of the study revealed that they are small or localized on the molecular surface, regardless of the phenotype. Coloring of affected atoms based on distances between wild type and mutant ones clearly showed the characteristic structural changes in the GLA protein geographically and subquantitatively. Structural investigation is useful for elucidation of the basis of Fabry disease and predicting disease outcome.

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Section: Amino Acid Substitutions Causing Classic and Variant Fabry Dmentioning

confidence: 99%

Structural characterization of mutant α-galactosidases causing Fabry disease

et al. 2008

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“…The root-mean-square graduate value was set at 0.05 kcal/mol Å . Then, each mutant model was superimposed on the wild-type structure based on the Ca atoms by the least-square-mean fitting method (Kabsch 1976(Kabsch , 1978Sakuraba et al 2000Sakuraba et al , 2004Matsuzawa et al 2003Matsuzawa et al , 2005. We defined that the structure was influenced by an amino acid substitution when the position of an atom in a mutant differed from that in the wild type by more than the cutoff distance (0.15 Å ) based on the total RMSD, as described previously (Matsuzawa et al 2005).…”

Section: Introductionmentioning

confidence: 99%

Structural study on mutant α-l-iduronidases: insight into mucopolysaccharidosis type I

et al. 2008

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To elucidate the basis of mucopolysaccharidosis type I (MPS I), we constructed structural models of mutant a-L-iduronidases (IDUAs) resulting from 33 amino acid substitutions that lead to MPS I (17 severe, eight intermediate, and eight attenuated). Then, we examined the structural changes in the enzyme protein by calculating the number of atoms affected and determined the root-meansquare distance (RMSD) and the solvent-accessible surface area (ASA). In the severe MPS I group, the number of atoms influenced by a mutation and the average RMSD value were larger than those in the attenuated group, and the residues associated with the mutations identified in the severe group tended to be less solvent accessible than those in the attenuated group. The clinically intermediate phenotype group exhibited intermediate values for the numbers of atoms affected, RMSD, and ASA between those in the severe group and those in the attenuated group. The results indicated that large structural changes had occurred in the core region in the severe MPS I group and small ones on the molecular surface in the attenuated MPS I group. Color imaging revealed the distributions and degrees of the structural changes caused by representative mutations for MPS I. Thus, structural analysis is useful for elucidating the basis of MPS I. As there was a difference in IDUA structural change between the severe MPS I group and the attenuated one, except for a couple of mutations, structural analysis can help predict the clinical outcome of the disease.

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“…[2,3] In addition to a broad range of carcinomas, [3,4] Tn expression has been reported during development/embryogenesis, [5][6][7] in pathogenic parasites, [8,9] on HIV-1, [10] and in a variety of rare human diseases such as Tn syndrome, [11] IgA Nephropathy, [12] Henoch-Schonlein purpura, [13] and Schindler-Kanzaki disease. [14,15] However, expression in normal adult tissue is rare. As a result, there has been significant interest in monitoring expression of the Tn antigen for diagnostic purposes as well as developing Tn-based vaccines for cancer and HIV.…”

Section: Introductionmentioning

confidence: 99%

Carbohydrate Array Analysis of Anti‐Tn Antibodies and Lectins Reveals Unexpected Specificities: Implications for Diagnostic and Vaccine Development

Manimala

Jain³

et al. 2005

ChemBioChem

103

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The Tn antigen is a carbohydrate antigen expressed in most carcinomas, during embryogenesis, on pathogenic parasites, and on HIV. It has been evaluated extensively as a potential diagnostic marker and several Tn-based vaccines are in clinical trials. Based on discrepancies in the literature regarding Tn expression, we began to question whether antibodies and lectins used routinely to detect the Tn antigen were providing accurate information. To investigate this possibility, a carbohydrate microarray and a highly sensitive assay were developed and three frequently used Tn receptors (HBTn1, Bric111, and VVL-B4) were evaluated. Carbohydrate-array analysis revealed unexpected cross-reactivity with other human carbohydrate epitopes. VVL-B4 bound the Tn antigen, GalNAcalpha1-6Gal, and GalNAcalpha1-3Gal. Bric111 bound the Tn antigen, blood group A, GalNAcalpha1-6Gal, and GalNAcalpha1-3Gal. HBTn1 showed the best selectivity, but still displayed moderate binding to blood group A. Implications for the development of Tn-based diagnostics and vaccines are discussed.

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Structural and immunocytochemical studies on α-N-acetylgalactosaminidase deficiency (Schindler/Kanzaki disease)

Cited by 44 publications

References 28 publications

Structural characterization of mutant α-galactosidases causing Fabry disease

Structural characterization of mutant α-galactosidases causing Fabry disease

Structural study on mutant α-l-iduronidases: insight into mucopolysaccharidosis type I

Carbohydrate Array Analysis of Anti‐Tn Antibodies and Lectins Reveals Unexpected Specificities: Implications for Diagnostic and Vaccine Development

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