Active Site Dynamical Effects in the Hydrogen Transfer Rate-limiting Step in the Catalysis of Linoleic Acid by Soybean Lipoxygenase-1 (SLO-1): Primary and Secondary Isotope Contributions.
Active Site Dynamical Effects in the Hydrogen Transfer Rate-limiting Step in the Catalysis of Linoleic Acid by Soybean Lipoxygenase-1 (SLO-1): Primary and Secondary Isotope Contributions.
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大豆脂氧合酶-1 (SLO-1) 催化亚油酸过程中氢转移速率限制步骤中的活性位点动力学效应：主要和次要同位素贡献。
DOI：
10.1021/acs.jpcb.5b02385
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Iyengar,SrinivasanS
中科院分区：
文献类型：
--
作者：
Phatak,Prasad;Venderley,Jordan;Debrota,John;Li,Junjie;Iyengar,SrinivasanS
使用从头分子动力学（AIMD）模拟，促进罕见事件的治疗，我们探测的活性位点参与的速率决定氢转移步骤中的催化氧化亚油酸的大豆脂氧合酶-1（SLO-1）。两个不同的活性部位组件的作用进行了探讨。(a)在活性位点的氢原子受体侧上，受体侧羟基（其与铁辅因子结合）和异亮氨酸的骨架羧基（残基编号839）之间的氢键结合倾向被研究朝向其在促进氢转移事件中的作用。研究了初级和次级（H/D）同位素效应，发现与次级H/D同位素效应有一定的相关性，随着平均核动能的增加，由于I839骨架羰基与受体氧之间存在氢键，转移几率增加。平均核动能的进一步增加降低了这种二级氢键的强度，这导致氢转移速率的恶化，并最终表现出类似Arrhenius的行为。(b)在氢原子供体侧，主要定位在供体侧亚油酸基团和反应模式的振动模式之间的耦合进行了探测。对于氢和氘转移，属于亚油酸的模式和氢转移模式之间的耦合似乎存在质的差异。例如，与氢转移的情况相比，供体侧仲氢原子在氘转移期间更不稳定（接近5倍）。这似乎表明属于亚油酸支架的模式和氘转移模式之间的更大耦合，并且还为克纳普、里克特和克林曼在J. Am.化学会，2002，124，3865。为了证实我们在上述a点中的发现，我们提出了I839 → A839或I839 → V839突变。这将改变键合残基中氢的体积，从而允许在上文强调的二级氢键形成中具有更大的灵活性，并对反应速率产生不利影响。
Usingab initiomolecular dynamics (AIMD) simulations that facilitate the treatment of rare events, we probe the active site participation in the rate-determining hydrogen transfer step in the catalytic oxidation of linoleic acid by soybean lipoxygenase-1 (SLO-1). The role of two different active site components is probed. (a) On the hydrogen atom acceptor side of the active site, the hydrogen bonding propensity between the acceptor side hydroxyl group, which is bound to the iron cofactor, and the backbone carboxyl group of isoleucine (residue number 839) is studied toward its role in promoting the hydrogen transfer event. Primary and secondary (H/D) isotope effects are also probed and a definite correlation with subtle secondary H/D isotope effects is found. With increasing average nuclear kinetic energy, the increase in transfer probability is enhanced due to the presence of the hydrogen bond between the backbone carbonyl of I839 and the acceptor oxygen. Further increase in average nuclear kinetic energy reduces the strength of this secondary hydrogen bond which leads to a deterioration in hydrogen transfer rates and finally embrances an Arrhenius-like behavior. (b) On the hydrogen atom donor side, the coupling between vibrational modes predominantly localized on the donor-side linoleic acid group and the reactive mode is probed. There appears to be a qualitative difference in the coupling between modes that belong to linoleic acid and the hydrogen transfer mode, for hydrogen and deuterium transfer. For example, the donor side secondary hydrogen atom is much more labile (by nearly a factor of 5) during deuterium transfer as compared to the case for hydrogen transfer. This appears to indicate a greater coupling between the modes belonging to the linoleic acid scaffold and the deuterium transfer mode and also provides a new rationalization for the abnormal (nonclassical) secondary isotope effect results obtained by Knapp, Rickert, and Klinman in J. Am. Chem. Soc., 2002, 124, 3865. To substantiate our findings noted in point a above, we have suggested an I839 → A839 or I839 → V839 mutation. This will modify the bulkiness of hydrogen the bonding residue, allowing greater flexibility in the secondary hydrogen bond formation highlighted above and adversely affecting the reaction rate.
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影响因子：
3
作者：
Lehnert, N;Solomon, EI
通讯作者：
Solomon, EI
影响因子：
1.8
作者：
J. Klinman
通讯作者：
J. Klinman
影响因子：
4.4
作者：
Iyengar, SS
通讯作者：
Iyengar, SS
“泵-探针”原子中心密度矩阵传播研究，用于测量大气反应加合物中的非和谐性和能量重新分配：OH 异戊二烯和 OH 丁二烯反应中间体的案例研究。
DOI：
10.1021/jp212330e
发表时间：
2012
期刊：
The journal of physical chemistry. A
影响因子：
--
作者：
Alexander B. Pacheco;Scott M. Dietrick;P. Stevens;S. Iyengar
通讯作者：
S. Iyengar
DOI：
10.1021/j100207a001
发表时间：
1982
期刊：
The Journal of Physical Chemistry
影响因子：
--
作者：
C. Parmenter
通讯作者：
C. Parmenter