title: The importance of arginine mutation for the evolutionary structure and function of phenylalanine hydroxylase gene.
abstract: Phenylalanine hydroxylase (PAH) gene mutations were investigated in 23 (46 alleles) unrelated phenylketonuria (PKU) patients in Cukurova region. First, all exons of PAH gene were screened by denaturing high performance liquid chromatography (DHPLC), and then, the suspicious samples were analyzed by direct sequencing technique. Consequently, the following results were obtained: IVS10-11g-->a splicing mutation in 27/46 (58.7%), R261Q mutation in 7/46 (15.2%) and E178G, R243X, R243Q, P281L, Y386C, R408W mutations, each found in the frequency of 2/46 (4.3%). In many countries, Arginine mutations have the highest frequency among PAH gene mutations in PKU patients. Although, CpG dinucleotids are effective in mutations resulting in arginine changes, this finding originated from the studies on the causes of mutations rather than the studies on the importance of arginine amino acid. In our analyses, we have detected that a majority of mutations causing a change in arginine and other amino acids concentrated in exon 7 comprising the catalytic domain (residues 143-410) of PAH gene. Several studies has emphasized the role of arginine amino acid; with the following outcomes; arginine repetition is significant for RNA binding proteins, and for histon proteins in eukaryotic gene expression, and also arginine repetition occurring in the structure of signal recognition particle's (SRPs) as a consequence of post-translational processes is very important in terms of gene expression. Therefore, the role of arginine amino acid in PAH gene is rather remarkable in that it shows the role of amino acids in the protein/RNA interaction that has started in the evolutionary process and is still preserved and maintained in the motif formation of active domain structure due to its strong binding properties. Thus, such properties imply that both arginine amino acid and exon 7 is of great significance with regards to the structure and function of the PheOH enzyme.
authors.affiliation: University of Cukurova, Faculty of Medicine, Department of Medical Biology and Genetics, Adana, Turkey. ululeyap@mail.cu.edu.tr
authors.forename: H Umit
authors.initials: HU
authors.lastname: Lüleyap
authors.forename: Davut
authors.initials: D
authors.lastname: Alptekin
authors.forename: Ayfer
authors.initials: A
authors.lastname: Pazarbaşi
authors.forename: Mulkiye
authors.initials: M
authors.lastname: Kasap
authors.forename: Halil
authors.initials: H
authors.lastname: Kasap
authors.forename: Hakan
authors.initials: H
authors.lastname: Demirhindi
authors.forename: Neslihan
authors.initials: N
authors.lastname: Mungan
authors.forename: Güler
authors.initials: G
authors.lastname: Ozer
authors.forename: Ursula G
authors.initials: UG
authors.lastname: Froster
mesh_terms: D000483:Alleles; D001120:Arginine / Q000235:genetics*; D002851:Chromatography, High Pressure Liquid; D004252:DNA Mutational Analysis / Q000379:methods; D005091:Exons / Q000235:genetics; D005787:Gene Frequency; D006801:Humans; D009154:Mutation / Q000235:genetics*; D010651:Phenylalanine Hydroxylase / Q000235:genetics*; D010661:Phenylketonurias / Q000201:enzymology / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics; D014421:Turkey
chemical_list: D001120:Arginine; D010651:Phenylalanine Hydroxylase