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

1)还原型细胞色素c氧化酶（CcO）催化氧分子四电子还原为两个水分子。尽管实验学家提出了许多不同的反应机理，但反应机理仍然没有定论。本课题尝试用CcO研究酶反应机理，完成了从氧分子生成第一个水分子的机理研究。总之，a）水通过氢键存在于His 290和Tyr 244之间。该水是连接Tyr 244（法呢基乙基）和Thr 316（K通道的末端）的氢键网络的末端分子。可以合理地认为，质子通过氢键网络转移到该水分子上，从而产生氧分子的还原。B）通过质子转移形成的水合氢离子移动到血红素a3的分子氧结合Fe原子。在质子转移到Fe-OO得到FeOOH后，水分子回到与H氢键结合的原始位置 ...更多信息 是290和Tyr 244。换句话说，这个水分子对于质子传递到还原活性位点起着重要作用。c）在质子移动的同时，CuB位的Cu原子转移一个电子，使Cu原子的电子结构从一价变为二价。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氢键转移到His 290和Tyr 244。f）在质子转移期间，两个电子从血红素a转移到活性位点，从而形成水分子。本课题采用B3 LYP方法对细胞色素c氧化酶催化氧分子还原反应机理进行了理论计算。2）实验观察表明，Cu介导下，G_1在5 '-XG_1G_2G_3-3'（X=T或C）中被选择性损伤。本课题以鸟嘌呤为配位基，研究了Cu（I）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三重态的G_1-选择性是由Cu（I）与5 ′-XG_1G_2G_3- 3 ′的G_2-选择性配位引起的。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