Coupling of hydrogenic tunneling to active-site motion in the hydrogen radical transfer catalyzed by a coenzyme B12-dependent mutase
Coupling of hydrogenic tunneling to active-site motion in the hydrogen radical transfer catalyzed by a coenzyme B12-dependent mutase
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DOI：
10.1073/pnas.0702188104
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发表时间：
2007-06-26
影响因子：
11.1
通讯作者：
Truhlar, Donald G.
中科院分区：
文献类型：
--
作者：
Dybala-Defratyka, Agnieszka;Paneth, Piotr;Truhlar, Donald G.
由辅酶 B-12 依赖性甲基丙二酰辅酶 A 变位酶催化的氢转移反应具有非常大的动力学同位素效应，表明它们通过高度量子隧道机制进行。我们通过结合量子力学/分子力学势和半经典量子动力学计算来解释动力学同位素效应。多维隧道效应将计算出的固有氢动力学同位素效应的幅度提高了 3.6 倍，从 14 增加到 51，与实验结果非常吻合。这些计算证实，隧道效应的贡献可能足够大，甚至可以解释> 50的动力同位素效应，这不是因为势垒异常薄，而是因为切角隧道效应减少了系统隧道的距离，而有效势垒或隧道效应的有效质量却没有相应增加。
Hydrogen transfer reactions catalyzed by coenzyme B-12-dependent methylmalonyl-CoA mutase have very large kinetic isotope effects, indicating that they proceed by a highly quantal tunneling mechanism. We explain the kinetic isotope effect by using a combined quantum mechanical/molecular mechanical potential and semiclassical quantum dynamics calculations. Multidimensional tunneling increases the magnitude of the calculated intrinsic hydrogen kinetic isotope effect by a factor of 3.6 from 14 to 51, in excellent agreement with experimental results. These calculations confirm that tunneling contributions can be large enough to explain even a kinetic isotope effect > 50, not because the barrier is unusually thin but because corner-cutting tunneling decreases the distance over which the system tunnels without a comparable increase in either the effective potential barrier or the effective mass for tunneling.