Sadeghian, Keyarash and Bocola, Marco and Merz, Thomas and Schuetz, Martin (2010) Theoretical Study on the Repair Mechanism of the (6-4) Photolesion by the (6-4) Photolyase. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 132 (45). pp. 16285-16295. ISSN 0002-7863,
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UV irradiation of DNA can lead to the formation of mutagenic (6-4) pyrimidine-pyrimidone photolesions. The (6-4) photolyases are the enzymes responsible for the photoinduced repair of such lesions. On the basis of the recently published crystal structure of the (6-4) photolyase bound to DNA [Maul et al. 2008] and employing quantum mechanics/molecular mechanics techniques, a repair mechanism is proposed, which involves two photoexcitations. The flavin chromophore, initially being in its reduced anionic form, is photoexcited and donates an electron to the (6-4) form of the photolesion. The photolesion is then protonated by the neighboring histidine residue and forms a radical intermediate. The latter undergoes a series of energy stabilizing hydrogen-bonding rearrangements before the electron back transfer to the flavin semiquinone. The resulting structure corresponds to the oxetane intermediate, long thought to be formed upon DNA-enzyme binding. A second photoexcitation of the flavin promotes another electron transfer to the oxetane. Proton donation from the same histidine residue allows for the splitting of the four-membered ring, hence opening an efficient pathway to the final repaired form. The repair of the lesion by a single photoexcitation was shown not to be feasible.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ELECTRON-TRANSFER; DNA PHOTOLYASE; CRYSTAL-STRUCTURE; QM/MM METHODS; FAD COFACTOR; DIMER REPAIR; FORCE-FIELD; AB-INITIO; THYMINE; OXETANE; |
| Subjects: | 500 Science > 540 Chemistry & allied sciences 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie Chemistry and Pharmacy > Institut für Physikalische und Theoretische Chemie > Research Group Theoretical Chemistry > Prof. Dr. Martin Schütz |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 06 Jul 2020 10:56 |
| Last Modified: | 06 Jul 2020 10:56 |
| URI: | https://pred.uni-regensburg.de/id/eprint/23871 |
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