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Substrate-mediated proton relay mechanism for the religation reaction in topoisomerase II
Kyohei Hanaoka1, Mitsuo Shoji, Daiki Kondo
1a Graduate School of Pure and Applied Sciences, University of Tsukuba , Tennodai 1-1-1, Tsukuba , 305-8571 , Japan .
Abstract:
The DNA religation reaction of yeast type II topoisomerase (topo II) was investigated to elucidate its metal-dependent general acid/base catalysis. Quantum mechanical/molecular mechanical calculations were performed for the topo II religation reaction, and the proton transfer pathway was examined. We found a substrate-mediated proton transfer of the topo II religation reaction, which involves the 3' OH nucleophile, the reactive phosphate, water, Arg781, and Tyr782. Metal A stabilizes the transition states, which is consistent with a two-metal mechanism in topo II. This pathway may be required for the cleavage/religation reaction of topo IA and II and will provide a general explanation for the catalytic mechanism in the topo IA and II.
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