Molecular modeling of O6-methylguanine-DNA methyltransferase mutant proteins encoded by single nucleotide polymorphisms

  • Authors:
    • Sonja M. Schwarzl
    • Jeremy C. Smith
    • Bernd Kaina
    • Thomas Efferth
  • View Affiliations

  • Published online on: October 1, 2005     https://doi.org/10.3892/ijmm.16.4.553
  • Pages: 553-557
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Abstract

The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) acts as a chemoprotectant and mediates resistance to alkylating anti-tumor agents. A number of MGMT single nucleotide polymorphisms (SNPs) have been described. We analyzed by molecular modeling the regions likely to be affected in the MGMT mutant proteins encoded by SNPs. Starting from the crystal structure of non-alkylated MGMT, molecular models of mutant proteins encoded by SNPs have been built. Most of the mutations were found to be located either within the DNA binding region (A121E, A121T, G132R, N123V) or in the vicinity of the active Cys145 (I143V, G160R). A further L84F mutant might affect Zn2+ binding. W65C was found to possibly be unstable.

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October 2005
Volume 16 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Schwarzl SM, Smith JC, Kaina B and Efferth T: Molecular modeling of O6-methylguanine-DNA methyltransferase mutant proteins encoded by single nucleotide polymorphisms. Int J Mol Med 16: 553-557, 2005
APA
Schwarzl, S.M., Smith, J.C., Kaina, B., & Efferth, T. (2005). Molecular modeling of O6-methylguanine-DNA methyltransferase mutant proteins encoded by single nucleotide polymorphisms. International Journal of Molecular Medicine, 16, 553-557. https://doi.org/10.3892/ijmm.16.4.553
MLA
Schwarzl, S. M., Smith, J. C., Kaina, B., Efferth, T."Molecular modeling of O6-methylguanine-DNA methyltransferase mutant proteins encoded by single nucleotide polymorphisms". International Journal of Molecular Medicine 16.4 (2005): 553-557.
Chicago
Schwarzl, S. M., Smith, J. C., Kaina, B., Efferth, T."Molecular modeling of O6-methylguanine-DNA methyltransferase mutant proteins encoded by single nucleotide polymorphisms". International Journal of Molecular Medicine 16, no. 4 (2005): 553-557. https://doi.org/10.3892/ijmm.16.4.553