Overexpression of recombinant human antiquitin in E. coli: partial enzyme activity in selected ALDH7A1 missense mutations associated with pyridoxine-dependent epilepsy.
Mol Genet Metab
; 111(4): 462-6, 2014 Apr.
Article
em En
| MEDLINE
| ID: mdl-24613284
ABSTRACT
Pyridoxine-dependent epilepsy (PDE) is an autosomal recessive disorder characterized by early onset seizures responsive to pyridoxine and caused by a defect in the α-aminoadipic semialdehyde dehydrogenase (antiquitin) gene (ALDH7A1). We selected four PDE-associated missense ALDH7A1 mutations, p.V367F, p.F410L, p.Q425R, and p.C450S, generated them in a recombinant human antiquitin cDNA with expression in E. coli at either 30°C or 37°C. One mutation, p.C450S, demonstrated substantial activity after expression at both temperatures, potentially contributing to milder biochemical and clinical phenotypes. The p.Q425R mutation yielded no activity at either temperature. The other two mutations yielded significant enzymatic activity at 30°C and markedly reduced activity at 37°C. For these latter three mutations, the markedly reduced or absent enzymatic activity resulting from expression at 37°C may be consistent with pathogenicity.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Recombinantes
/
Mutação de Sentido Incorreto
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Aldeído Desidrogenase
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Epilepsia
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article