A possible overestimation of the effect of acetylation on lysine residues in KQ mutant analysis
Copyright © 2011 Wiley Periodicals, Inc.
| Veröffentlicht in: | Journal of computational chemistry. - 1984. - 33(2012), 3 vom: 30. Jan., Seite 239-46 |
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| 1. Verfasser: | |
| Weitere Verfasser: | , , , , , , , , , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2012
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| Zugriff auf das übergeordnete Werk: | Journal of computational chemistry |
| Schlagworte: | Journal Article Research Support, Non-U.S. Gov't Antigens, Nuclear DNA-Binding Proteins DNA 9007-49-2 Ku Autoantigen EC 4.2.99.- Lysine K3Z4F929H6 |
| Zusammenfassung: | Copyright © 2011 Wiley Periodicals, Inc. Acetylation of lysine residues, one of the most common protein post-transcriptional modifications, is thought to regulate protein affinity with other proteins or nucleotides. Experimentally, the effects of acetylation have been studied using recombinant mutants in which lysine residues (K) are substituted with glutamine (Q) as a mimic of acetyl lysine (KQ mutant), or with arginine (R) as a mimic of nonacetylated lysine (KR mutant). These substitutions, however, have not been properly validated. The effects lysine acetylation on Ku, a multifunctional protein that has been primarily implicated in DNA repair and cell survival, are characterized herein using a series of computer simulations. The binding free energy was reduced in the KQ mutant, while the KR mutant had no effect, which is consistent with previous experimental results. Unexpectedly, the binding energy between Ku and DNA was maintained at almost the same level as in the wild type protein despite full acetylation of the lysine residues. These results suggest that the effects of acetylation may be overestimated when the KQ mutant is used as a mimic of the acetylated protein |
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| Beschreibung: | Date Completed 03.04.2012 Date Revised 25.11.2016 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1096-987X |
| DOI: | 10.1002/jcc.21956 |