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

Olufsen, Magne

dc.contributor.advisor	Smalås, Arne O.
dc.contributor.advisor	Brandsdal, Bjørn Olav
dc.contributor.author	Olufsen, Magne
dc.date.accessioned	2019-02-19T12:23:58Z
dc.date.available	2019-02-19T12:23:58Z
dc.date.issued	2007-05-25
dc.description.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 (k<sub>cat</sub> and K<sub>m</sub>) 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.	en_US
dc.identifier.uri	https://hdl.handle.net/10037/14719
dc.language.iso	eng	en_US
dc.publisher	Universitetet i Tromsø	en_US
dc.publisher	University of Tromsø	en_US
dc.relation.haspart	<p>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 <i>N</i>-glycosylase (UNG) from Atlantic Cod (<i>Gadus morhua</i>). (Article in press). The article is available in the thesis introduction. Published version in <i>Journal of Molecular Biology, 343</i>(5), 1221-1230, is available at <a href=https://doi.org/10.1016/j.jmb.2004.09.004>https://doi.org/10.1016/j.jmb.2004.09.004. </a><p> <p>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. <i>Journal of biological chemistry, 280</i>, 18042-18048. Also available at <a href=https://doi.org/10.1074/jbc.M500948200>https://doi.org/10.1074/jbc.M500948200. </a><p> <p>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 <i>Journal of Molecular Graphics and Modelling, 26</i>(1), 124-134, is available at <a href=https://doi.org/10.1016/j.jmgm.2006.10.003> https://doi.org/10.1016/j.jmgm.2006.10.003. </a>. <p> <p>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 <i>Proteins, 71</i>(3), 1219-1230, is available at <a href=https://doi.org/10.1002/prot.21815>https://doi.org/10.1002/prot.21815. </a><p> <p>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 <i>Journal of Molecular Modeling, 14</i>(3), 201-213, is available at <a href=https://doi.org/10.1007/s00894-007-0261-0>https://doi.org/10.1007/s00894-007-0261-0. </a><p>	en_US
dc.rights.accessRights	openAccess	en_US
dc.rights.holder	Copyright 2007 The Author(s)
dc.rights.uri	https://creativecommons.org/licenses/by-nc-sa/3.0	en_US
dc.rights	Attribution-NonCommercial-ShareAlike 3.0 Unported (CC BY-NC-SA 3.0)	en_US
dc.subject	VDP::Mathematics and natural science: 400::Chemistry: 440	en_US
dc.subject	VDP::Matematikk og Naturvitenskap: 400::Kjemi: 440	en_US
dc.title	The molecular origin of cold adaptation: A comparative study of cold- and warm-active uracil DNA glycosylase	en_US
dc.type	Doctoral thesis	en_US
dc.type	Doktorgradsavhandling	en_US