Overexpression of human antiquitin in E. coli: enzymatic characterization of twelve ALDH7A1 missense mutations associated with pyridoxine-dependent epilepsy.

Abstract:

:Pyridoxine dependent epilepsy 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). In order to characterize the effects of a series of twelve disease-associated ALDH7A1 missense mutations on antiquitin activity, we generated the mutations in a recombinant human antiquitin cDNA and expressed them in Escherichia coli. We developed an automated spectrophotometric assay of antiquitin enzymatic activity using the natural substrate α-aminoadipic semialdehyde. The substrate was generated using a recombinant lysine aminotransferase gene (lat) from Streptomyces clavuligerus. In the E. coli expression system all the mutants were stably expressed but lacked enzymatic activity. This is consistent with pathogenicity of these mutations in vivo.

journal_name

Mol Genet Metab

authors

Coulter-Mackie MB,Li A,Lian Q,Struys E,Stockler S,Waters PJ

doi

10.1016/j.ymgme.2012.06.008

subject

Has Abstract

pub_date

2012-08-01 00:00:00

pages

478-81

issue

4

eissn

1096-7192

issn

1096-7206

pii

S1096-7192(12)00244-2

journal_volume

106

pub_type

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