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ANALIZA UTICAJA MUTACIJE p.Gln226Lys U GENU ZA FENILALANIN HIDROKSILAZU
(PAH) NA STRUKTURU I FUNKCIJU PROTEINA PAH POMOĆU BIOINFORMATIĈKIH
SOFTVERA

ANALYSIS OF THE IMPACT OF p.Gln226Lys MUTATION IN THE PHENYLALANINE
HYDROXYLASE GENE (PAH) ON THE STRUCTURE AND FUNCTION OF PAH PROTEIN
USING BIOINFORMATICS SOFTWARE

Autor: Jovana Lazarević Užička gimnazija-Ivgodina Regionalni centar za talente Beograd II

Mentor: Dr Kristel Klaassen, naučni saradnik

REZIME
Fenilketonurija (PKU) je monogenska bolest koja predstavlja jedan od najčešćih naslednih
poremećaja metabolizma aminokiselina. Nasleđuje se autozomno recesivno i uzrokovana je
mutacijama u genu za fenilalanin hidroksilazu (PAH). Mutacije u genu PAH dovode do
izmenjene strukture i/ili funkcije enzima, koji za krajnju posledicu ima tešku i irverzibilnu
mentalnu retardaciju. Cilj ovog rada bila je predikcija efekta mutacije p.Gln226Lys u genu PAH
korišćenjem različitih bioinformatičkih softvera. PolyPhen-2, SIFT i MutPred su krorišćeni za
predikciju efekta mutacija na strukturu i funkciju proteina. Proteinski model je analiziran uz
pomoć Swiss-PdbViewer programa. Korišćenjem Clustal Omega softvera ispitivana je evolutivna
očuvanost izmenjenih aminokiselina. Svi korišćeni softveri ukazuju da se radi o mutaciji koja
najverovatnije dovodi do teške kliničke slike. Rezultate je neophodno potvrditi funkcionalnom
analizom mutacije.
Kljuĉne reĉi: bioinformatički softveri, gen za fenilalanin hidroksilazu, fenilketonurija, mutacije

SUMMARY
Phenylketonuria (PKU) is a monogenic disease and presents one of the most common inborn
disorders of amino acid metabolism. It is inherited in an autosomal recessive manner and it is
caused by mutations in the phenylalanine hydroxylase (PAH) gene. Mutations in the PAH gene
lead to an altered structure and/or function of the enzyme, thus leading to elevated level of blood
phenylalanine, which finally results in severe and irreversible mental retardation. The aim of this
study was to predict the effect of p.Gln226Lys mutation in the PAH gene using various
bioinformatics software programs. PolyPhen-2, SIFT and MutPred were used to predict the effect
of mutations on the structure and function of the protein. The protein model was analyzed with
Swiss-PdbViewer program. The evolutionary preservation of altered amino acids was tested by
using Clustal Omega software. All used software programs suggest that the mutation most
probably leads to severe clinical manifestations. The results ought to be confirmed by performing
functional analysis of the mutation.
Key words: bioinformatics software programs, mutations, phenylalanine hydroxylase gene,
phenylketonuria