Compound I of nitric oxide synthase: The active site protonation state
Compound I of nitric oxide synthase: The active site protonation state
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DOI：
10.1021/ja066662r
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发表时间：
2007-03-21
影响因子：
15
通讯作者：
Shaik, Sason
中科院分区：
文献类型：
--
作者：
Cho, Kyung-Bin;Derat, Etienne;Shaik, Sason
对从含氧亚铁中间体形成一氧化氮合酶 (NOS) 的难以捉摸的活性物质化合物 I (Cpd I) 的量子力学/分子力学 (QM/MM) 研究表明，必须提供两个质子才能产生合理放热的反应，并导致四氢生物蝶呤辅因子上出现自由基。分子动力学和能量考虑表明，质子的可能来源是从表面到活性位点形成的水氢键链，但水分子本身不能成为质子的来源；沿着链传播的 H3O+ 物质更有可能。 QM/MM 计算表明，Cpd I 和 H2O 是由铁-过氧化氢复合物以独特的异裂 O-O 裂解机制形成的。将如此形成的 Cpd I 的特性与已知种类的氯过氧化物酶的特性进行比较，发现几何形状和自旋密度是兼容的。计算出穆斯堡尔参数，并可作为尝试表征 NOS Cpd I 的实验探针。
A quantum mechanical/molecular mechanical (QM/MM) study of the formation of the elusive active species Compound I (Cpd I) of nitric oxide synthase (NOS) from the oxyferrous intermediate shows that two protons have to be provided to produce a reaction that is reasonably exothermic and that leads to the appearance of a radical on the tetrahydrobiopterin cofactor. Molecular dynamics and energy considerations show that a possible source of proton is the water H-bond chain formed from the surface to the active site, but that a water molecule by itself cannot be the source of the proton; an H3O+ species that is propagated along the chain is more likely. The QM/MM calculations demonstrate that Cpd I and H2O are formed from the ferric-hydrogen peroxide complex in a unique heterolytic O-O cleavage mechanism. The properties of the so-formed Cpd I are compared with those of the known species of chloroperoxidase, and the geometry and spin densities are found to be compatible. The Mossbauer parameters are calculated and may serve as experimental probes in attempts to characterize NOS Cpd I.