Comparative study of structural changes caused by different substitutions at the same residue on α-galactosidase A.

Missense mutations in the α-galactosidase A (GLA) gene comprising the majority of mutations responsible for Fabry disease result in heterogeneous phenotypes ranging from the early onset severe "classic" form to the "later-onset" milder form. To elucidate the molecular basis of Fa...

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Autores principales:	Seiji Saito, Kazuki Ohno, Hitoshi Sakuraba
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d40fbeb4682a45fe9b53e669f8fd40a1
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spelling	oai:doaj.org-article:d40fbeb4682a45fe9b53e669f8fd40a12021-11-18T08:40:17ZComparative study of structural changes caused by different substitutions at the same residue on α-galactosidase A.1932-620310.1371/journal.pone.0084267https://doaj.org/article/d40fbeb4682a45fe9b53e669f8fd40a12013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24386359/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Missense mutations in the α-galactosidase A (GLA) gene comprising the majority of mutations responsible for Fabry disease result in heterogeneous phenotypes ranging from the early onset severe "classic" form to the "later-onset" milder form. To elucidate the molecular basis of Fabry disease from the viewpoint of structural biology, we comprehensively examined the effects of different substitutions at the same residue in the amino acid sequence of GLA on the structural change in the enzyme molecule and the clinical phenotype by calculating the number of atoms affected and the root-mean-square-distance value, and by coloring of the atoms influenced by the amino acid replacements. The results revealed that the severity of the structural change influences the disease progression, i.e., a small structural change tends to lead to the later-onset form and a large one to the classic form. Furthermore, the study revealed the residues important for expression of the GLA activity, i.e., residues involved in construction of the active site, a disulfide bond or a dimer. Structural study from such a viewpoint is useful for elucidating the basis of Fabry disease.Seiji SaitoKazuki OhnoHitoshi SakurabaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 12, p e84267 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Seiji Saito Kazuki Ohno Hitoshi Sakuraba Comparative study of structural changes caused by different substitutions at the same residue on α-galactosidase A.
description	Missense mutations in the α-galactosidase A (GLA) gene comprising the majority of mutations responsible for Fabry disease result in heterogeneous phenotypes ranging from the early onset severe "classic" form to the "later-onset" milder form. To elucidate the molecular basis of Fabry disease from the viewpoint of structural biology, we comprehensively examined the effects of different substitutions at the same residue in the amino acid sequence of GLA on the structural change in the enzyme molecule and the clinical phenotype by calculating the number of atoms affected and the root-mean-square-distance value, and by coloring of the atoms influenced by the amino acid replacements. The results revealed that the severity of the structural change influences the disease progression, i.e., a small structural change tends to lead to the later-onset form and a large one to the classic form. Furthermore, the study revealed the residues important for expression of the GLA activity, i.e., residues involved in construction of the active site, a disulfide bond or a dimer. Structural study from such a viewpoint is useful for elucidating the basis of Fabry disease.
format	article
author	Seiji Saito Kazuki Ohno Hitoshi Sakuraba
author_facet	Seiji Saito Kazuki Ohno Hitoshi Sakuraba
author_sort	Seiji Saito
title	Comparative study of structural changes caused by different substitutions at the same residue on α-galactosidase A.
title_short	Comparative study of structural changes caused by different substitutions at the same residue on α-galactosidase A.
title_full	Comparative study of structural changes caused by different substitutions at the same residue on α-galactosidase A.
title_fullStr	Comparative study of structural changes caused by different substitutions at the same residue on α-galactosidase A.
title_full_unstemmed	Comparative study of structural changes caused by different substitutions at the same residue on α-galactosidase A.
title_sort	comparative study of structural changes caused by different substitutions at the same residue on α-galactosidase a.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/d40fbeb4682a45fe9b53e669f8fd40a1
work_keys_str_mv	AT seijisaito comparativestudyofstructuralchangescausedbydifferentsubstitutionsatthesameresidueonagalactosidasea AT kazukiohno comparativestudyofstructuralchangescausedbydifferentsubstitutionsatthesameresidueonagalactosidasea AT hitoshisakuraba comparativestudyofstructuralchangescausedbydifferentsubstitutionsatthesameresidueonagalactosidasea
_version_	1718421471224659968

Comparative study of structural changes caused by different substitutions at the same residue on α-galactosidase A.

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