DNA Repair Mechanism by Photolyase: Electron Transfer Path from the Photolyase Catalytic Cofactor FADH−to DNA Thymine Dimer
| Autor: | Alexei A. Stuchebrukhov, Dmitry M. Medvedev |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Models
Molecular Statistics and Probability DNA Repair Dimer Pyrimidine dimer Flavin group Photochemistry General Biochemistry Genetics and Molecular Biology Electron Transport Electron transfer chemistry.chemical_compound Catalytic Domain Escherichia coli Animals Computer Simulation Photolyase General Immunology and Microbiology Applied Mathematics General Medicine Electron transport chain Thymine chemistry Biochemistry Pyrimidine Dimers Modeling and Simulation Flavin-Adenine Dinucleotide General Agricultural and Biological Sciences Deoxyribodipyrimidine Photo-Lyase DNA |
| Zdroj: | Journal of Theoretical Biology. 210:237-248 |
| ISSN: | 0022-5193 |
| DOI: | 10.1006/jtbi.2001.2291 |
| Popis: | Photolyase is an enzyme that catalyses photorepair of thymine dimers in UV damaged DNA by electron transfer reaction. The structure of the photolyase/DNA complex is unknown at present. Using crystal structure coordinates of the substrate-free enzyme from E. coli, we have recently built a computer molecular model of a thymine dimer docked to photolyase catalytic site and studied molecular dynamics of the system. In this paper, we present analysis of the electronic coupling and electron transfer pathway between the catalytic cofactor FADH(-) and the pyrimidine dimer by the method of interatomic tunneling currents. Electronic structure is treated in the extended Hückel approximation. The root mean square transfer matrix element is about 6 cm(-1), which is consistent with the experimentally determined rate of transfer. We find that electron transfer mechanism responsible for the repair utilizes an unusual folded conformation of FADH(-) in photolyases, in which the isoalloxazine ring of the flavin and the adenine are in close proximity, and the peculiar features of the docked orientation of the dimer. The tunneling currents show explicitly that despite of the close proximity between the donor and acceptor complexes, the electron transfer mechanism between the flavin and the thymine bases is not direct, but indirect, with the adenine acting as an intermediate. These calculations confirm the previously made conclusion based on an indirect evidence for such mechanism. |
| Databáze: | OpenAIRE |
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