Implications of a Water Molecule for Photoactivation of Plant (6–4) Photolyase

Photolyases (PLs) are flavoproteins able to repair crosslinks formed between adjacent pyrimidine bases in DNA in a light-dependent manner via an electron transfer. The catalytically-active redox state of the flavin chromophore for the DNA repair is a fully-reduced form of flavin adenine dinucleotide, FADH–. PLs and its relevant, cryptochromes (CRYs), share a physicochemical process attributable to light-dependent reduction of the chromophore via an ultrafast successive electron transfer through exclusively conserved three tryptophan side chains. In some (6–4) PLs and animal CRYs, an additional tryptophan participates in this photoactivation process. In a search for the intrinsic difference between the Trp triad and tetrad, a water molecule proximal to Trp was found in the reported crystal structure of Arabidopsis thaliana (6–4) PL. Here, we investigated the involvement of the water molecule in the photoactivation. Molecular dynamics simulations indicated that the water is stably captured in the binding si...