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Ion pairs and their role in modulating stability of cold‐ and warm‐active uracil DNA glycosylase
Author(s) -
Olufsen Magne,
Papaleo Elena,
Smalås Arne Oskar,
Brandsdal Bjørn Olav
Publication year - 2007
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.21815
Subject(s) - uracil dna glycosylase , dna glycosylase , uracil , dna , ion , chemistry , biophysics , biology , dna repair , biochemistry , organic chemistry
MD simulations and continuum electrostatics calculations have been used to study the observed differences in thermostability of cold‐ and warm‐active uracil DNA glycosylase (UDG). The present study focuses on the role of ion pairs and how they affect the thermal stability of the two enzymes. Analysis of the MD generated structural ensembles show that cod UDG (cUDG) and human UDG (hUDG) have 11 and 12 ion pairs which are present in at least 30% of the conformations. The electrostatic contribution of the ion pairs, computed using continuum electrostatics, is slightly more favorable in cUDG at 298 K. This is primarily attributed to more optimized interactions between the ion pairs and nearby dipoles/charges in cUDG. More global salt bridges are found in hUDG and are more stabilizing when compared to cUDG, possibly playing a role in maintaining overall stability and reducing conformational entropy. Both enzymes contain one three‐member ionic network, but the one found in hUDG is far more stabilizing. Our results also suggest that care should be taken when performing statistical analysis of crystal structures with respect to ion pairs, and that crystallization conditions must be carefully examined when performing such analysis. Proteins 2008. © 2007 Wiley‐Liss, Inc.