D. Medvedev et Aa. Stuchebrukhov, DNA repair mechanism by photolyase: Electron transfer path from the photolyase catalytic cofactor FADH(-) to DNA thymine dimer, J THEOR BIO, 210(2), 2001, pp. 237-248
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 t
he substrate-free enzyme from E. coil, we have recently built a computer mo
lecular model of a thymine dimer docked to photolyase catalytic site and st
udied molecular dynamics of the system. In this paper, we present analysis
of the electronic coupling and electron transfer pathway between the cataly
tic cofactor FADH(-) and the pyrimidine dimer by the method of interatomic
tunneling currents. Electronic structure is treated in the extended Huckel
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 utili
zes an unusual folded conformation of FADH- in photolyases, in which the is
oalloxazine 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 d
onor and acceptor complexes, the electron transfer mechanism between the fl
avin and the thymine bases is not direct, but indirect, with the adenine ac
ting as an intermediate. These calculations confirm the previously made con
clusion based on an indirect evidence for such mechanism. (C) 2001 Academic
Press.