Harran Üniversitesi Tıp Fakültesi Dergisi

Yazarlar: Müzeyyen İZMİRLİ, Atilla AKDEMİR, Bülent GÖGEBAKAN, Davut ALPTEKİN

Konular:-

Anahtar Kelimeler:5,10 methylenetetrahydrofolate,10 methylenetetrahydrofolate reductase,Flavin-Adenine Dinucleotide

Özet: Backgrounds: The enzyme known as eukaryotic methylenetetrahydrofolate reductase (MTHFR) and consists of 656 amino acids, has a homodimer structure. Each units of this enzyme consists of catalytic and regulator areas. For the catalytic activity of this enzyme, FAD must be connected with MTHFR by noncovalent bonds. The gene of human MTHFR enzyme is localized at chromosome 1p36.3. A C>T transition at nucleotide position 677 is located in the fourth exon of the MTHFR gene which results the conversion of alanine to valine at codon 222 of the protein. We aimed to form a model about the crystal structure of MTHFR because of there is no study about the crystal structure of the protein that put forth. In addition, we aimed to put forth the changes in the crystal structure of MTHFR by Ala222Val change as a result of MTHFR 677C>Tpolymorphism. Methods: To this end, we used MOE computer programme as molecular modeling techniques (version 2013.0801, Chemical Computing Group Inc., Montreal, Canada). Results: We saw that the bonds between MTHFR enzyme in human and FAD are over the amino acids Tyr50, Gly108, Asp109, Tyr149, Arg107, Ala127, Lys169 Tyr126, His153 and His165 and the double bond between Tyr126 and His165 may be because of the compression feature. Conclusions: Consequently, a model has set forth about the crystal structure of MTHFR in human and because of the Ala222val changes affect the status of the FAD binding, to influence the enzyme activity was determined.

---