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Biochemistry (Moscow)

, Volume 79, Issue 1, pp 31–36 | Cite as

In silico study of effects of polymorphisms on biophysical chemical properties of oxidized N-terminal domain of X-ray cross-complementing group 1 protein

  • J. MehrzadEmail author
  • M. Monajjemi
  • M. Hashemi
Article
  • 103 Downloads

Abstract

Base excision repair (BER) is the major pathway involved in removal of endogenous and mutagen-induced DNA damage. The X-ray cross-complementing group 1 protein (XRCC1), which participates in BER, is a scaffolding protein. The oxidized XRCC1 N-terminal domain (NTD) forms additional interactions with DNA polymerase β (Pol β). Any change in the residues of a protein (XRCC1, XRCC4, etc.) may alter its stability and function. Many coding regions of genes have single nucleotide polymorphisms (SNPs) that change the conformation of their products, and they are probably involved in some diseases. The R7L and R107H mutations are located in the XRCC1-NTD. In the present study, biophysical chemical properties of oxidized XRCC1-NTD (wild type or mutants) were investigated at different temperatures (290, 295, 298, 301, 304, 309, 310, 311, and 312 K) in water using in silico molecular mechanic computational methods. Comparison of the average calculated potential energies of oxidized XRCC1-NTD reveals that the R7L mutation increases stability, but the R107H and R7L&R107H mutations are destabilizing. Therefore, mutant types of this protein (R107H or R7L&R107H) may not function correctly. Furthermore, quantitative structure-activity relationship (QSAR) of oxidized XRCC1-NTD and docking assay showed that the R7L mutation is advantageous but the R107H and R7L&R107H mutations are disadvantageous for XRCC1-NTD, and in the latter cases it cannot interact with Pol β as well as the wild type does. Hence, DNA repair may be defective. Also, using the equation dE = ∂E/(∂T)V·dT + ∂E/(∂V)T·dV, it was determined that the best temperature for normal activity of oxidized XRCC1-NTD is exactly the natural body temperature (310 K).

Key words

XRCC1 NTD polymorphism in silico QSAR docking dE 

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Copyright information

© Pleiades Publishing, Ltd. 2014

Authors and Affiliations

  1. 1.Department of Biochemistry, Neyshabur BranchIslamic Azad UniversityNeyshaburIran
  2. 2.Department of Chemistry, Science and Research BranchIslamic Azad UniversityTehranIran
  3. 3.Department of Clinical Biochemistry, School of MedicineZahedan University of Medical SciencesZahedanIran

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