title: Substrate-mediated proton relay mechanism for the religation reaction in topoisomerase II.
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.
authors.affiliation: a Graduate School of Pure and Applied Sciences, University of Tsukuba , Tennodai 1-1-1, Tsukuba , 305-8571 , Japan .
authors.forename: Kyohei
authors.initials: K
authors.lastname: Hanaoka
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Shoji
authors.forename: Daiki
authors.initials: D
authors.lastname: Kondo
authors.forename: Akimasa
authors.initials: A
authors.lastname: Sato
authors.forename: Moon Young
authors.initials: MY
authors.lastname: Yang
authors.forename: Katsumasa
authors.initials: K
authors.lastname: Kamiya
authors.forename: Kenji
authors.initials: K
authors.lastname: Shiraishi
mesh_terms: D001120:Arginine / Q000737:chemistry; D055162:Biocatalysis; D004250:DNA Topoisomerases, Type II / Q000737:chemistry*; D017665:Hydroxyl Radical / Q000737:chemistry; D008958:Models, Molecular; D011522:Protons; D011789:Quantum Theory; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry*; D013379:Substrate Specificity; D014443:Tyrosine / Q000737:chemistry
chemical_list: D011522:Protons; D029701:Saccharomyces cerevisiae Proteins; D017665:Hydroxyl Radical; D014443:Tyrosine; D001120:Arginine; D004250:DNA Topoisomerases, Type II
keywords: DNA religation; QM/MM study; catalytic mechanism; proton transfer; topoisomerase II