The PKU mutation S349P causes complete loss of catalytic activity in the recombinant phenylalanine hydroxylase enzyme.
The mutation S349P in exon 10 of the phenylalanine hydroxylase (PAH) gene was identified in one Norwegian and one Polish phenylketonuria (PKU) allele on a haplotype 1.7 background. This missense mutation in PAH codon 349 is a T to C transition in cDNA position 1267. This mutation has been reported both on haplotype 1 and 4, suggesting recurrent mutation. In two different expression systems, the pET and the pMAL systems of Escherichia coli, it was shown that the S349P mutation, introduced by site directed mutagenesis, results in complete loss of enzymatic activity. Thus, protein instability alone does not seem to be the direct cause of the lack of activity of this PKU mutation as previously reported.
Knappskog
P M
PM
Department of Medical Genetics, Haukeland Hospital, Bergen, Norway.
Eiken
H G
HG
Martinez
A
A
Flatmark
T
T
Apold
J
J
D001483:Base Sequence; D015870:Gene Expression; D006239:Haplotypes; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010651:Phenylalanine Hydroxylase / Q000235:genetics*; D010661:Phenylketonurias / Q000235:genetics*; D016133:Polymerase Chain Reaction
D010651:Phenylalanine Hydroxylase