The molecular origin of cold adaptation: A comparative study of cold- and warm-active uracil DNA glycosylase

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Thesis introduction, paper I + paper III (PDF)
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Date
2007-05-25
Type
Doctoral thesis
Doktorgradsavhandling

Author
Olufsen, Magne
Abstract
During the last decade or so, scientists at the Norwegian Structural Biology Centre (NorStruct) have used the enzyme uracil DNA glycosylase (UDG) as a model system in the study of cold-adaptation, protein-DNA recognition and enzyme specificity. The cod UDG (cUDG) and human UDG (hUDG) are thoroughly biologically characterized and there are established well-functioning recombinant expression systems to produce mutants. More than 30 mutants of cUDG and hUDG have been expressed, purified and characterized. The kinetic constants (kcat and Km) have been obtained for the majority of these mutants. In addition, the crystal structure has been determined for some of them. This Ph.D. project is an extension of earlier work done at NorStruct.
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Paper I: Moe, E., Leiros, I., Riise, E.K., Olufsen, M., Lanes, O., Smalås, A.O. & Willassen, N.P. (2004). Optimisation of the Surface Electrostatics as a Strategy for Cold Adaptation of Uracil-DNA N-glycosylase (UNG) from Atlantic Cod (Gadus morhua). (Article in press). The article is available in the thesis introduction. Published version in Journal of Molecular Biology, 343(5), 1221-1230, is available at https://doi.org/10.1016/j.jmb.2004.09.004.

Paper II: Olufsen, M., Smalås, A.O., Moe, E. & Brandsdal, B.O. (2005). Increased flexibility as a strategy for cold adaptation – A comparative molecular dynamics study of cold- and warm-active uracil DNA glycosylase. Journal of biological chemistry, 280, 18042-18048. Also available at https://doi.org/10.1074/jbc.M500948200.

Paper III: Olufsen, M., Brandsdal, B.O. & Smalås, A.O. (2007). Comparative unfolding studies of psychrophilic and mesophilic uracil DNA glycosylase: MD simulations show reduced thermal stability of the cold-adapted enzyme. (Article in press). The article is available in the thesis introduction. Published version in Journal of Molecular Graphics and Modelling, 26(1), 124-134, is available at https://doi.org/10.1016/j.jmgm.2006.10.003. .

Paper IV Olufsen, M., Papaleo, E., Smalås, A.O. & Brandsdal, B.O. Ion pairs and their role in modulating stability of cold- and warm-active uracil DNA glycosylase. (Submitted manuscript). Published version in Proteins, 71(3), 1219-1230, is available at https://doi.org/10.1002/prot.21815.

Paper V: Olufsen, M., Smalås, A.O. & Brandsdal, B.O. Electrostatic interactions play an essential role in DNA repair and cold-adaptation of Uracil DNA Glycosylase. (Manuscript). Published version in Journal of Molecular Modeling, 14(3), 201-213, is available at https://doi.org/10.1007/s00894-007-0261-0.

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Universitetet i Tromsø
University of Tromsø
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