Effect of D۲۲۶N point mutation on the structure of the enzyme IMPDH۱ in comparison with the wild type
سال انتشار: 1399
نوع سند: مقاله کنفرانسی
زبان: انگلیسی
مشاهده: 134
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شناسه ملی سند علمی:
BIOCONF21_0692
تاریخ نمایه سازی: 7 شهریور 1400
چکیده مقاله:
IMPDH is one of the protected enzymes in prokaryotes and eukaryotes. The function of this enzyme is in de novo biosynthesis of purine nucleotides. Mammals have two homologues of the IMPDH gene, named IMPDH۱ and IMPDH۲. Retinal isoforms of the enzyme IMPDH۱ were detected in the retina of humans and mice. Mutations associated with retinitis pigmentosa (RP) have been discovered in the IMPDH۱ gene and new functions have been demonstrated for it. IMPDH۱ enzyme function in the retina is disrupted by R۲۲۴P and D۲۲۶N point mutations and RP disease develops. Based on the description given, we decided to study this enzyme structurally. Therefore, after cloning the wild type IMPDH۱, expression and purification of both isoforms ۵۱۴ and ۵۴۶ and cloning of mutant type D۲۲۶N, expression and purification of mutant isoform ۵۱۴, we studied the structural properties of this enzyme by using Gel Filtration Chromatography technique. According to the chromatographic results, the mutant isoforms form extremely large structures compared to the wild type. The wild type of enzyme in the presence of ATP / GTP causes octameric structures with enhanced enzyme activity. While the presence of a mycophenolic acid inhibitor causes the formation of extremely large inactive macromolecules. It seems that the presence of C-terminal sequence in the retinal isoform has increased the sensitivity of this isoform to conditions. This structural adjustment directly affects or inhibits enzyme activity. To better understand this issue, it is necessary to conduct more studies on retinal and canonical isoforms of this enzyme.
کلیدواژه ها:
نویسندگان
Maryam Khaledikia
Faculty of basic sciences, University of Mazandaran, Mazandaran, Iran
Razieh Yazdanparast
Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran
Bager Seyedalipour
Faculty of basic sciences, University of Mazandaran, Mazandaran, Iran