Theoretical Study of Enzyme Reaction and DNA DamageMediated by Transition Metal Ion

点击翻译按钮获取中文摘要

1) Reduced cytochrome c oxidase (CcO) catalyses four-electron reduction of oxygen molecule to two water molecules. The reaction mechanism is not still conclusive, although experimentalists have proposed many different mechanisms. In this project, we have tried to study the mechanism of enzyme reaction by CcO, ad have completed study of mechanism yielding first water molecule from oxygen molecule. In summary, a) water exists between His290 and Tyr244 through hydrogen bonding. This water is a terminal molecule of network of hydrogen bonding connecting Tyr244, farnesylethyl, and Thr316, a terminal of K-channel. It is reasonable to think that a proton is transferred to this water molecule through the hydrogen-bonded network to yield the reduction of oxygen molecule. b) Hydronium ion formed by the proton transfer moves to molecular oxygen binding Fe atom of heme a3. After the proton is shifted to Fe-OO to give FeOOH, the water molecule goes back to the original position hydrogen-bonded to H … More is 290 and Tyr244. In other word, this water molecule plays an important role for proton deliver into reduction active site. c) An electron is transferred from Cu atom of CuB site to at the same time of an proton shift, yielding the change of electronic structure of Cu atom from monovalent to divalent. d) The activation energy of the proton transfer is estimated to be 12 kcal/mole under condition without molecular oxygen binding Fe atom. e) second proton necessary to form water molecule is also transferred by the water molecule hydrogen-bonding to His290 and Tyr244. f) Two electrons are transferred to the active site from heme a during the proton transfer, yielding the formation of the water molecule. In this project, we have completed the reduction mechanism of oxygen molecule catalyzed by fully reduce cytochrome c oxidase using the theoretical calculations of B3LYP method. Future project is to elucidate the mechanism yielding second water molecule.2) Experimental observation proposed that G_1 in 5'-XG_1G_2G_3-3' (X=T or C) is selectively damaged under condition of Cu-mediation. In this project, we investigated relative stabilities and electronic structures of the Cu-coordinated 5'-XG_1G_2G_3-3' and their cation radicals based on the structure of guanine coordinated by Cu(l) ion. we have concluded that the G_1-selectivity of GGG triplet is induced by the G_2-selective coordination of Cu(l) to 5'-XG_1G_2G_3-3'. Less