Electron-transfer induced repair of 6-4 photoproducts in DNA: A computational study

被引:35
作者
Borg, O. Anders
Eriksson, Leif A.
Durbeej, Bo
机构
[1] Univ Siena, Dept Chem, I-53100 Siena, Italy
[2] Uppsala Univ, Dept Quantum Chem, S-75120 Uppsala, Sweden
[3] Univ Orebro, Orebro Life Sci Ctr, S-70182 Orebro, Sweden
[4] Univ Orebro, Dept Nat Sci, S-70182 Orebro, Sweden
关键词
D O I
10.1021/jp0676383
中图分类号
O64 [物理化学(理论化学)、化学物理学];
学科分类号
070304 ; 081704 ;
摘要
The mechanism employed by DNA photolyase to repair 6-4 photoproducts in UV-damaged DNA is explored by means of quantum chemical calculations. Considering the repair of both oxetane and azetidine lesions, it is demonstrated that reduction as well as oxidation enables a reversion reaction by creating anionic or cationic radicals that readily fragment into monomeric pyrimidines. However, on the basis of calculated reaction energies indicating that electron transfer from the enzyme to the lesion is a much more favorable process than electron transfer in the opposite direction, it is suggested that the photoenzymic repair can only occur by way of an anionic mechanism. Furthermore, it is shown that reduction of the oxetane facilitates a mechanism involving cleavage of the C-O bond followed by cleavage of the C-C bond, whereas reductive fragmentation of the azetidine may proceed with either of the intermonomeric C-N and C-C bonds cleaved as the first step. From calculations on neutral azetidine radicals, a significant increase in the free-energy barrier for the initial fragmentation step upon protonation of the carbonylic oxygens is predicted. This effect can be attributed to protonation serving to stabilize reactant complexes more than transition structures.
引用
收藏
页码:2351 / 2361
页数:11
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