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Femtochemistry in enzyme catalysis: DNA photolyase

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Abstract

Photolyase uses light energy to split UV-induced cyclobutane pyrimidine dimers in damaged DNA. This photoenzyme encompasses a series of elementary dynamical processes during repair function from early photoinitiation by a photoantenna molecule to enhance repair efficiency, to in vitro photoreduction through aromatic residues to reconvert the cofactor to the active form, and to final photorepair to fix damaged DNA. The corresponding series of dynamics include resonance energy transfer, intraprotein electron transfer, and intermolecular electron transfer, bond breaking-making rearrangements and back electron return, respectively. We review here our recent direct studies of these dynamical processes in real time, which showed that all these elementary reactions in the enzyme occur within subnanosecond timescale. Active-site solvation was observed to play a critical role in the continuous modulation of catalytic reactions. As a model system for enzyme catalysis, we isolated the enzyme–substrate complex in the transition-state region and mapped out the entire evolution of unmasked catalytic reactions of DNA repair. These observed synergistic motions in the active site reveal a perfect correlation of structural integrity and dynamical locality to ensure maximum repair efficiency on the ultrafast time scale.

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Acknowledgments

The work was supported in part by the Packard Foundation Fellowship to DZ and the National Institute of Health to AS and DZ.

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Authors and Affiliations

  1. Departments of Physics, Chemistry, and Biochemistry, Programs of Biophysics, Chemical Physics, and Biochemistry, The Ohio State University, Columbus, OH, 43210, USA

    Ya-Ting Kao, Chaitanya Saxena, Lijuan Wang & Dongping Zhong

  2. Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Mary Ellen Johns Building, CB 7260, Chapel Hill, NC, 27599, USA

    Aziz Sancar

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  1. Ya-Ting Kao
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  2. Chaitanya Saxena
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  4. Aziz Sancar
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Correspondence to Dongping Zhong.

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Kao, YT., Saxena, C., Wang, L. et al. Femtochemistry in enzyme catalysis: DNA photolyase. Cell Biochem Biophys 48, 32–44 (2007). https://doi.org/10.1007/s12013-007-0034-5

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