Characterization of Nucleobase-Amino Acid Stacking Interactions Utilized by a DNA Repair Enzyme
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- 作者：Lesley R. Rutledge ; Lachlan S. Campbell-Verduyn ; Ken C. Hunter ; Stacey D. Wetmore
- 刊名：Journal of Physical Chemistry B
- 出版年：2006
- 出版时间：October 5, 2006
- 年：2006
- 卷：110
- 期：39
- 页码：19652 - 19663
- 全文大小：533K
- 年卷期：v.110,no.39(October 5, 2006)
- ISSN：1520-5207
文摘
The present work characterizes the gas-phase stacking interactions between four aromatic amino acid residues(histidine, phenylalanine, tyrosine, and tryptophan) and adenine or 3-methyladenine due to the proposedutilization of these interactions by enzymes that repair DNA alkylation damage. The MP2 potential energysurfaces of the stacked dimers are considered as a function of four variables (vertical displacement, angle ofrotation, horizontal displacement, and tilt angle) using a variety of basis sets. It is found that the maximumstacking interaction energy decreases with the amino acid according to TRP > TYR 
HIS > PHE for bothnucleobases. However, the magnitude of the stacking interaction significantly increases upon alkylation (by50-115%). Comparison of the stacking energies calculated using our surface scans to those estimated fromexperimental crystal structures indicates that the stacking interactions within the active site of 3-methyladenineDNA glycosylase can account for 65-75% of the maximum possible stacking interaction between the relevantmolecules. The decrease in stacking in the crystal structure arises due to significant differences in the relativeorientations of the nucleobase and amino acid. Nevertheless, alkylation is found to significantly increase thestacking energy when the crystal structure geometries are considered. Our calculations provide computationalsupport for suggestions that alkylation enhances the stacking interactions within the active site of DNA repairenzymes, and they give a measure of the magnitude of this enhancement. Our results suggest that alkylationlikely plays a more important role in substrate identification and removal than the nature of the aromaticamino acid that interacts with the substrate via stacking interactions.
HIS > PHE for bothnucleobases. However, the magnitude of the stacking interaction significantly increases upon alkylation (by50-115%). Comparison of the stacking energies calculated using our surface scans to those estimated fromexperimental crystal structures indicates that the stacking interactions within the active site of 3-methyladenineDNA glycosylase can account for 65-75% of the maximum possible stacking interaction between the relevantmolecules. The decrease in stacking in the crystal structure arises due to significant differences in the relativeorientations of the nucleobase and amino acid. Nevertheless, alkylation is found to significantly increase thestacking energy when the crystal structure geometries are considered. Our calculations provide computationalsupport for suggestions that alkylation enhances the stacking interactions within the active site of DNA repairenzymes, and they give a measure of the magnitude of this enhancement. Our results suggest that alkylationlikely plays a more important role in substrate identification and removal than the nature of the aromaticamino acid that interacts with the substrate via stacking interactions.