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首页> 外文期刊>Journal of Natural Sciences Research >Path of Electron Transfer on Reaction of Xanthine Oxidase with 6-mercaptopurine and hypoxanthine
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Path of Electron Transfer on Reaction of Xanthine Oxidase with 6-mercaptopurine and hypoxanthine

机译：黄嘌呤氧化酶与6-巯基嘌呤和次黄嘌呤反应的电子转移途径

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Enzymes often rely on the coupling of electrons and protons to affect primary metabolic steps involving charge transport and catalysis. The present theoretical study is intend to explore the path of electron transfer from substrate to active site and to provide a plausible route of electron transfer in the enzymatic catalysis from 6-MP or hypoxanthine to active site. Density functional theory (DFT)/B3LYP method were used to probe the path of electron or proton transfer mechanism from Mullikan charge. The Mullikan atomic charge of Mo decreased from 0.624793 to 0.398834, CRH bound equatorial oxygen of active site is increased by 0.16132, HRH decreased by 0.146701 that is around two fold increase in electron density this may be due to removal of electron as hydride toward sulfido terminal. Terminal sulfido (SMo-HRH) decreased to -0.0107, Oeq of active site decreased to -0.43539 when it bound to C2 of substrate. The electronegativity of Oeq more than oxo group by 0.05154 hence Oeq is a better nucleophile. Therefore the catalytically labile site should be the metal-coordinated hydroxide (Oeq) rather than the apical oxo group (Mo=O). Sulfido terminal (SMo) decreased in electronegativity due to delocalization of electron density to active site Mo that facilitates the transfer of electron up on the attack of hydride from hydrogen bond substrate. Electron densities on Sfront and Sback increased in (-0.2233 & -0.20266) respectively which may facilitate the movement of equatorial hydroxide towards C2 of substrates (CRH). Charge distribution on C2 is (0.143402 and 0.139523) and on C8 is (0.140514 and 0.133494) respectively for 6-MP and hypoxanthine. This implies in both cases C2 shows electron deficiency and hence it is more electrophilic relative to C8. Charge density of HRH bound C2 is (0.171649 and 0.15786) and HRH bound C8 is (0.08821 and 0.080245) respectively for 6-MP and hypoxanthine hence hydrogen bound C2 is labile for hydride transfer due to high electronegative nature which indicate C2 position is more susceptible to nucleophilic attack by hydroxide of active site. Therefore it can be generalized that oxidation of 6-mercaptopurine or hypoxanthine by XO proceed through abstraction of proton by Glu1226 from equatorial hydroxide of active site followed by nucleophilic attach on C2 of substrate and hydride was transferred through concomitant release of oxidized substrate. Key words:hypoxanthine, 6-mercaptopurine, Density functional theory, nucleophile
机译：酶通常依赖电子和质子的耦合来影响涉及电荷传输和催化的主要代谢步骤。目前的理论研究旨在探索电子从底物转移到活性位点的途径，并为从6-MP或次黄嘌呤到活性位点的酶催化​​提供电子转移的可行途径。密度泛函理论（DFT）/ B3LYP方法被用来探测穆利坎电荷中电子或质子转移机理的路径。 Mo的Mullikan原子电荷从0.624793减少至0.398834，CRH结合的活性位点赤道氧增加0.16132，HRH减少0.146701，这是电子密度增加大约两倍的原因，这可能是由于氢化物向硫化物末端移出了电子。当末端硫基（SMo-HRH）与底物的C2结合时，其活性亚基（Seq）降至-0.0107，活性位点的当量（Oeq）降至-0.43539。 Oeq的电负性比羰基高0.05154，因此Oeq是更好的亲核试剂。因此，催化不稳定的位点应该是金属配位的氢氧化物（Oeq），而不是顶端的氧代基团（Mo = O）。硫醚末端（SMo）的电负性降低是由于电子密度向活性位Mo的离域，这促进了氢从氢键底物的攻击下电子向上转移。 Sfront和Sback上的电子密度分别增加（-0.2233和-0.20266），这可能有助于赤道氢氧化物向底物C2（CRH）的移动。对于6-MP和次黄嘌呤，C2上的电荷分布分别为（0.143402和0.139523），C8上的电荷分布为（0.140514和0.133494）。这意味着在两种情况下，C2都显示电子不足，因此相对于C8更具亲电子性。对于6-MP和次黄嘌呤，HRH结合的C2的电荷密度分别为（0.171649和0.15786），HRH结合的C8的电荷密度分别为（0.08821和0.080245），因此氢结合的C2由于高电负性而对氢化物的转移不稳定，这表明C2的位置更敏感会受到活性位点氢氧化物的亲核攻击。因此，可以概括地说，XO氧化6-巯基嘌呤或次黄嘌呤是通过Glu1226从活性位点的赤道氢氧化物提取质子，然后亲核附着在底物的C2上而进行的，氢化物通过伴随释放被氧化的底物而转移。关键词：次黄嘌呤，6-巯基嘌呤，密度泛函理论，亲核试剂

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