Free-Energy Landscape and Proton Transfer Pathways in Oxidative Deamination by Methylamine Dehydrogenase.
Free-Energy Landscape and Proton Transfer Pathways in Oxidative Deamination by Methylamine Dehydrogenase.
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甲胺脱氢酶氧化脱氨中的自由能景观和质子转移途径
DOI：
10.1002/cphc.201601113
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
D. Marx
中科院分区：
文献类型：
--
作者：
T. Zelleke;D. Marx
用QM/MM分子动力学加速模拟方法研究了细菌酶甲胺脱氢酶还原半反应中的速率决定步骤。不受多维反应子空间以外自由度限制的多维热自由能景观的产生映射了两条非常相似的路径，用于将质子转移到两个天冬氨酸羧基氧原子之一，分别称为OD1和OD2，它们分别与Thr122和Trp108氢键。尽管垂直于一维质子转移坐标有显著的大幅度运动，但由于施主-受主距离的起伏约为3 ä，发现两个质子转移通道的一维质子转移自由能轮廓与多维自由能面上的最小自由能路径基本相同。在甲胺脱氢酶中，质子转移到受体氧原子之一-OD2位-在动力学和热力学上都略有优势，大约2 −1。力学分析表明，Thr122β与OD1之间的氢键始终处于过渡态，与质子转移通道无关。布居分析证实，底物氧化获得的电子电荷在色氨酸色氨酸对苯二酚辅因子的环系内离域。
The rate‐determining step in the reductive half‐reaction of the bacterial enzyme methylamine dehydrogenase, which is proton abstraction from the native substrate methylamine, is investigated using accelerated QM/MM molecular dynamics simulations at room temperature. Generation of the multidimensional thermal free‐energy landscape without restriction of the degrees of freedom beyond a multidimensional reaction subspace maps two rather similar pathways for the underlying proton transfer to one of two aspartate carboxyl oxygen atoms, termed OD1 and OD2, which hydrogen bond with Thr122 and Trp108, respectively. Despite significant large‐amplitude motion perpendicular to the one‐dimensional proton transfer coordinate, due to fluctuations of the donor–acceptor distance of about 3 Å, it is found that the one‐dimensional proton transfer free‐energy profiles are essentially identical to the minimum free‐energy pathways on the multidimensional free‐energy landscapes for both proton transfer channels. Proton transfer to one of the acceptor oxygen atoms—the OD2 site—is slightly favored in methylamine dehydrogenase by approximately 2 kcal mol−1, both kinetically and thermodynamically. Mechanistic analyses reveal that the hydrogen bond between Thr122β and OD1 is always present in the transition state independently of the proton transfer channel. Population analysis confirms that the electronic charge gained upon oxidation of the substrate is delocalized within the ring systems of the tryptophan tryptophylquinone cofactor.
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使用波函数传播方法评估甲胺脱氢酶的动力学同位素效应
影响因子：
2.2
作者：
Gustavo Pierdominici;J. Palma
通讯作者：
J. Palma
酶催化氢转移反应中量子隧道效应的计算机模拟
DOI：
--
发表时间：
2010
期刊：
Interdisciplinary Sciences Computational Life Sciences
影响因子：
--
作者：
K. Ranaghan;A. Mulholland
通讯作者：
A. Mulholland
甲胺脱氢酶对甲胺去质子化的经典路径和量子路径分析。
影响因子：
2.9
作者：
K. Ranaghan;Laura Masgrau;N. Scrutton;M. Sutcliffe;A. Mulholland
通讯作者：
A. Mulholland
甲胺脱氢酶活性位点的分子动力学研究。
DOI：
10.1021/jp060715
发表时间：
2006
期刊：
The journal of physical chemistry. B
影响因子：
--
作者：
Gustavo Pierdominici;J. Echave;J. Palma
通讯作者：
J. Palma
影响因子：
15
作者：
Faulder, PF;Tresadern, G;Burton, NA
通讯作者：
Burton, NA