| Autor: |
Lipton AS; The Biological Sciences Directorate, Pacific Northwest National Laboratory, K8-98, 902 Battelle Boulevard, Richland, Washington 99352, USA., Heck RW, Primak S, McNeill DR, Wilson DM 3rd, Ellis PD |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of the American Chemical Society [J Am Chem Soc] 2008 Jul 23; Vol. 130 (29), pp. 9332-41. Date of Electronic Publication: 2008 Jun 25. |
| DOI: |
10.1021/ja0776881 |
| Abstrakt: |
Apurinic/apyrimidinic endonuclease 1 (APE1), a member of the divalent cation-dependent phosphoesterase superfamily of proteins that retain the conserved four-layered alpha/beta-sandwich structural core, is an essential protein that functions as part of base excision repair to remove mutagenic and cytotoxic abasic sites from DNA. Using low-temperature solid-state (25)Mg NMR spectroscopy and various mutants of APE1, we demonstrate that Mg(2+) binds to APE1 and a functional APE1-substrate DNA complex with an overall stoichiometry of one Mg(2+) per mole of APE1 as predicted by the X-ray work of Tainer and co-workers (Mol, C. D.; Kuo, C. F.; Thayer, M. M.; Cunningham, R. P.; Tainer, J. A. Nature 1995, 374 , 381-386). However, the NMR spectra show that the single Mg(2+) site is disordered. We discuss the probable reasons for the disorder at the Mg(2+) binding site. The most likely source of this disorder is arrangement of the protein-ligands about the Mg(2+) (cis and trans isomers). The existence of these isomers reinforces the notion of the plasticity of the metal binding site within APE1. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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