Biological relevance of charge transfer branching pathways in photolyases.
Phys Chem Chem Phys
; 21(31): 17072-17081, 2019 Aug 21.
Article
em En
| MEDLINE
| ID: mdl-31313765
ABSTRACT
The repair of sun-induced DNA lesions by photolyases is driven by a photoinduced electron transfer from a fully reduced FAD to the damaged DNA. A chain of several aromatic residues connecting FAD to solvent ensures the prior photoreduction of the FAD cofactor. In PhrA, a class III CPD photolyase, two branching tryptophan charge transfer pathways have been characterized. According to previous experiments, both pathways play a role in the FAD photoreduction. To provide a molecular insight to the charge transfer abilities of both pathways, we perform multiscales simulations where the protein motion and the positive charge are simultaneously propagated. Our computational approach reveals that one pathway drives a very fast charge transfer whereas the other pathway provides a very good thermodynamic stabilization of the positive charge. During the simulations, the positive charge firstly moves on the fast triad, while a reorganization of the close FADË- environment occurs. Then, backward transfers can lead to the propagation of the positive charge on the second pathway. After one nanosecond, we observe a nearly equal probability to find the charge at ending tryptophan of either pathway; eventually the charge distribution will likely evolve towards a charge stabilization on the last tryptophan of the slowest pathway. Our results highlight the role the protein environment, which manages the association of a kinetic and a thermodynamic pathways to trigger a fast and efficient FAD photoreduction.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Modelos Moleculares
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Desoxirribodipirimidina Fotoliase
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Reparo do DNA
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article