TY  - JOUR
AU  - Stojiljković, Maja
AU  - Perez, Belen
AU  - Desviat, Lourdes R.
AU  - Aguado, Cristina
AU  - Ugarte, Magdalena
AU  - Pavlović, Sonja
PY  - 2009
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/398
AB  - Phenylketonuria (PKU), the most frequent disorder of amino acid metabolism, is caused by mutations in human phenylalanine hydroxylase gene (PAH), leading to deficient enzyme activity. Previously reported but uncharacterized PAH gene mutation, p.S231F (c.692C  gt  T), was detected in Serbian patients with classical PKU. We analyzed p.S231F PAH protein in prokaryotic (Escherichia coli) and eukaryotic expression system (hepatoma cells). In both systems the mutant enzyme was unstable. Residual enzyme activity in vitro was similar to 1%. Mutation p.S231F PAH was not activated by pre-incubation with phenylalanine substrate. We found no GroEL/GroES chaperone effect and slightly positive effect of the (6R)-l-erythro-5,6,7,8-tetrahydrobiopterin (BH4) on the stabilization of the protein structure. Our findings were in accordance with severe patients' phenotypes. In conclusion, p.S231F should be classified as a functionally null PAH gene mutation as it drastically reduces stability and activity of the PAH enzyme in vitro.
PB  - Springer, New York
T2  - Protein Journal
T1  - The Missense p.S231F Phenylalanine Hydroxylase Gene Mutation Causes Complete Loss of Enzymatic Activity In Vitro
EP  - 299
IS  - 6
SP  - 294
VL  - 28
DO  - 10.1007/s10930-009-9194-z
ER  - 

@article{
author = "Stojiljković, Maja and Perez, Belen and Desviat, Lourdes R. and Aguado, Cristina and Ugarte, Magdalena and Pavlović, Sonja",
year = "2009",
abstract = "Phenylketonuria (PKU), the most frequent disorder of amino acid metabolism, is caused by mutations in human phenylalanine hydroxylase gene (PAH), leading to deficient enzyme activity. Previously reported but uncharacterized PAH gene mutation, p.S231F (c.692C  gt  T), was detected in Serbian patients with classical PKU. We analyzed p.S231F PAH protein in prokaryotic (Escherichia coli) and eukaryotic expression system (hepatoma cells). In both systems the mutant enzyme was unstable. Residual enzyme activity in vitro was similar to 1%. Mutation p.S231F PAH was not activated by pre-incubation with phenylalanine substrate. We found no GroEL/GroES chaperone effect and slightly positive effect of the (6R)-l-erythro-5,6,7,8-tetrahydrobiopterin (BH4) on the stabilization of the protein structure. Our findings were in accordance with severe patients' phenotypes. In conclusion, p.S231F should be classified as a functionally null PAH gene mutation as it drastically reduces stability and activity of the PAH enzyme in vitro.",
publisher = "Springer, New York",
journal = "Protein Journal",
title = "The Missense p.S231F Phenylalanine Hydroxylase Gene Mutation Causes Complete Loss of Enzymatic Activity In Vitro",
pages = "299-294",
number = "6",
volume = "28",
doi = "10.1007/s10930-009-9194-z"
}

Stojiljković, M., Perez, B., Desviat, L. R., Aguado, C., Ugarte, M.,& Pavlović, S.. (2009). The Missense p.S231F Phenylalanine Hydroxylase Gene Mutation Causes Complete Loss of Enzymatic Activity In Vitro. in Protein Journal
Springer, New York., 28(6), 294-299.
https://doi.org/10.1007/s10930-009-9194-z

Stojiljković M, Perez B, Desviat LR, Aguado C, Ugarte M, Pavlović S. The Missense p.S231F Phenylalanine Hydroxylase Gene Mutation Causes Complete Loss of Enzymatic Activity In Vitro. in Protein Journal. 2009;28(6):294-299.
doi:10.1007/s10930-009-9194-z .

Stojiljković, Maja, Perez, Belen, Desviat, Lourdes R., Aguado, Cristina, Ugarte, Magdalena, Pavlović, Sonja, "The Missense p.S231F Phenylalanine Hydroxylase Gene Mutation Causes Complete Loss of Enzymatic Activity In Vitro" in Protein Journal, 28, no. 6 (2009):294-299,
https://doi.org/10.1007/s10930-009-9194-z . .