The Missense p.S231F Phenylalanine Hydroxylase Gene Mutation Causes Complete Loss of Enzymatic Activity In Vitro
Samo za registrovane korisnike
2009
Autori
Stojiljković, MajaPerez, Belen
Desviat, Lourdes R.
Aguado, Cristina
Ugarte, Magdalena
Pavlović, Sonja
Članak u časopisu (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
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 o...f the PAH enzyme in vitro.
Ključne reči:
Phenylketonuria / Phenylalanine hydroxylase activity / Human phenylalanine hydroxylase gene mutation / Expression analysis / ChaperonesIzvor:
Protein Journal, 2009, 28, 6, 294-299Izdavač:
- Springer, New York
Finansiranje / projekti:
- Strukturalni elementi genoma u modulaciji fenotipa (RS-MESTD-MPN2006-2010-143051)
- Boehringer Ingelheim Fondation
DOI: 10.1007/s10930-009-9194-z
ISSN: 1572-3887
PubMed: 19629656
WoS: 000270192600005
Scopus: 2-s2.0-70349462935
Institucija/grupa
Institut za molekularnu genetiku i genetičko inženjerstvoTY - 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 . .