Abstract
A molecular dynamics (MD) simulation is performed on a DNA photolyase to study the conformational behavior of the photoactive cofactor flavin adenine dinucleotide (FAD) inside the enzyme pocket. A DNA photolyase is a highly efficient light-driven enzyme that repairs the UV-induced cyclobutane pyrimidine dimer in damaged DNA. In this work, the FAD conformational and dynamic changes were studied within the total complex structure of a DNA photolyase protein (containing FADH–, MTHF, and DNA molecules) embedded in a water solvent. We aimed to compare the conformational changes of the FAD cofactor and other constituent fragments of the molecular system under consideration. The obtained results were discussed to gain insight into the light-driven mechanism of DNA repair by a DNA photolyase enzyme—based on the enzyme structure, the FAD mobility, and conformation shape.
Highlights
One of the most common lesions of living organisms induced by the UV irradiation of DNA—causing a number of harmful effects, such as growth delay, mutagenesis, and cell death—is a photoreaction of pyrimidine bases [1]
0.0697 0.0737 –0.5852 1.8105 –0.8064 0.5190 –0.8083 –0.8278 1.8425 –0.8044 0.5090 –0.8393 –0.6102 0.1664 0.0787 0.0707 0.0641 0.0887 –0.4066 0.0921 –0.6208 0.4360 0.1047 0.0821 –0.5718 0.4170 0.1217 0.2168 0.1407 –0.2940 0.3877 0.0688 –0.5261 –0.2432 0.7672 –0.9505 0.4488 0.4508 –0.7850 0.6999 0.0611 –0.7370 0.4808 second time scale in the molecular system under consideration: a photolyase enzyme, two cofactors (FADH and MTHF) fitted into the pocket, and DNA chain located in the vicinity of the enzyme; surrounded by water mole
molecular dynamics (MD) simulations were performed on the DNA photolyase ments of the DNA photolyase were built, and the comparison of the positional dynamics indicates different relative mobility
Summary
One of the most common lesions of living organisms induced by the UV irradiation of DNA—causing a number of harmful effects, such as growth delay, mutagenesis, and cell death—is a photoreaction of pyrimidine bases [1]. Thymine dimers (TT, cyclobutane pyrimidine dimers (CPDs)) could be formed after photon absorption by a thymine monomer, followed by its excitation state and subsequent reaction with an adjacent thymine molecule. Another type of DNA damage is the formation of the pyrimidine-pyrimidone (6-4) photo-prod-. Uct (T[]T) [1,2,3] Both of these lesions are repaired by DNA photolyases—enzyme proteins with similar structures and reaction mechanisms. The DNA photolyase enzyme repairs UV-induced DNA damage by splitting the ring of the predominant photoproduct—the cis,synCPD—into the corresponding pyrimidine monomers [17].
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