| Characterization of nucleobase-amino acid stacking interactions utilized by a DNA repair enzyme. | |
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MedLine Citation:
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PMID: 17004834 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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 proposed utilization of these interactions by enzymes that repair DNA alkylation damage. The MP2 potential energy surfaces of the stacked dimers are considered as a function of four variables (vertical displacement, angle of rotation, horizontal displacement, and tilt angle) using a variety of basis sets. It is found that the maximum stacking interaction energy decreases with the amino acid according to TRP > TYR approximately HIS > PHE for both nucleobases. However, the magnitude of the stacking interaction significantly increases upon alkylation (by 50-115%). Comparison of the stacking energies calculated using our surface scans to those estimated from experimental crystal structures indicates that the stacking interactions within the active site of 3-methyladenine DNA glycosylase can account for 65-75% of the maximum possible stacking interaction between the relevant molecules. The decrease in stacking in the crystal structure arises due to significant differences in the relative orientations of the nucleobase and amino acid. Nevertheless, alkylation is found to significantly increase the stacking energy when the crystal structure geometries are considered. Our calculations provide computational support for suggestions that alkylation enhances the stacking interactions within the active site of DNA repair enzymes, and they give a measure of the magnitude of this enhancement. Our results suggest that alkylation likely plays a more important role in substrate identification and removal than the nature of the aromatic amino acid that interacts with the substrate via stacking interactions. |
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Authors:
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Lesley R Rutledge; Lachlan S Campbell-Verduyn; Ken C Hunter; Stacey D Wetmore |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The journal of physical chemistry. B Volume: 110 ISSN: 1520-6106 ISO Abbreviation: J Phys Chem B Publication Date: 2006 Oct |
Date Detail:
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Created Date: 2006-09-28 Completed Date: 2007-08-17 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101157530 Medline TA: J Phys Chem B Country: United States |
Other Details:
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Languages: eng Pagination: 19652-63 Citation Subset: IM |
Affiliation:
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Department of Chemistry, Mount Allison University, 63C York Street, Sackville, New Brunswick, Canada E4L 1G8. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenine
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analogs & derivatives,
chemistry Amino Acids / chemistry* Binding Sites Biophysics / methods* Chemistry, Physical / methods* Crystallization DNA / chemistry* DNA Repair* Models, Chemical Models, Molecular Molecular Conformation Nucleic Acid Conformation Nucleotides / chemistry* Thermodynamics |
| Chemical | |
Reg. No./Substance:
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0/Amino Acids; 0/Nucleotides; 5142-23-4/3-methyladenine; 73-24-5/Adenine; 9007-49-2/DNA |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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