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

1)还原的细胞色素c氧化酶(CcO)催化氧分子四电子还原为两个水分子。尽管实验者提出了许多不同的机制，但反应机制仍不是决定性的。在本项目中，我们尝试研究了CCOO与酶反应的机理，并完成了氧分子生成第一水分子的机理研究。综上所述，a)水以氢键的形式存在于His290和Tyr244之间。这种水是连接Tyr244、法尼乙基和K-通道末端Thr316的氢键网络的末端分子。认为质子通过氢键网络转移到这个水分子上，产生氧分子的还原是合理的。B)质子转移形成的氢离子迁移到分子氧结合的铁原子上。在质子转移到Fe-OO生成FeOOH后，水分子回到原来的位置，氢键与H…结合更多的是290和244。换言之，这种水分子对质子输送到还原活性中心起着重要的作用。C)在质子移动的同时，一个电子从CuB位的铜原子转移到铜原子上，导致铜原子的电子结构由单价转变为二价。D)在没有分子氧结合Fe原子的条件下，质子转移的活化能估计为12千卡/摩尔。E)形成水分子所需的第二质子也通过水分子的氢键转移到His290和Tyr244上。F)在质子转移过程中，两个电子从血红素a转移到活性中心，产生水分子。在本项目中，我们用B3LYP方法进行了理论计算，完成了细胞色素c氧化酶完全还原催化氧分子还原的机理。2)实验观察表明，在铜的作用下，5‘-XG_1G_2G_3-3’(X=T或C)中的G_1受到选择性损伤。在这个项目中，我们基于与铜(L)配位的鸟嘌呤的结构，研究了铜配位的5‘-xG_1G_2G_3-3’及其阳离子自由基的相对稳定性和电子结构。我们认为GGG三联体的G_1选择性是由铜(L)与5‘-XG_1G_2G_3-3’的G_2选择性配位引起的。较少

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