Changes in protein architecture and subpicosecond protein dynamics impact the reaction catalyzed by lactate dehydrogenase.
Changes in protein architecture and subpicosecond protein dynamics impact the reaction catalyzed by lactate dehydrogenase.
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蛋白质结构的变化和亚秒蛋白动力学影响乳酸脱氢酶催化的反应。
DOI：
10.1021/jp400376h
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发表时间：
2013-08-15
期刊：
影响因子：
--
通讯作者：
Schwartz SD
中科院分区：
文献类型：
--
作者：
Masterson JE;Schwartz SD
我们之前已经确定了促进振动的重要性，这是一种亚微微秒的蛋白质运动，在乳酸脱氢酶（LDH）的反应坐标中通过特定的残基轴传播。为了测试这种运动的扰动会对酶促反应的影响，我们采用过渡路径采样，以获得过渡路径合奏四个独立的LDH酶系统：野生型酶，一个版本的酶表达重同位素取代，和两个酶与突变的促进振动轴。我们发现，即使是轻微的变化，促进振动的LDH结果在酶化学的显着变化。在“重”的版本的酶，我们发现，从重同位素取代的亚皮秒动力学的阻尼导致的势垒跨越的时间急剧增加。此外，我们看到，促进振动轴的突变导致酶促反应可用的过渡路径的可变性降低。综合结果揭示了LDH的蛋白质结构在酶催化中的重要性，通过建立促进振动是如何微调，以促进化学。
We have previously established the importance of a promoting vibration, a sub-picosecond protein motion that propagates through a specific axis of residues, in the reaction coordinate of lactate dehydrogenase (LDH). To test the effect that perturbation of this motion would have on the enzymatic reaction, we employ transition path sampling to obtain transition path ensembles for four independent LDH enzymatic systems: the wild type enzyme, a version of the enzyme expressing heavy isotopic substitution, and two enzymes with mutations in the promoting vibration axis. We show that even slight changes in the promoting vibration of LDH result in dramatic changes in enzymatic chemistry. In the “heavy” version of the enzyme, we find that the dampening of the sub-picosecond dynamics from heavy isotopic substitution leads to a drastic increase in the time of barrier crossing. Furthermore, we see that mutation of the promoting vibration axis causes a decrease in the variability of transition paths available to the enzymatic reaction. The combined results reveal the importance of the protein architecture of LDH in enzymatic catalysis by establishing how the promoting vibration is finely tuned to facilitate chemistry.
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影响因子：
15
作者：
Alexandrova, Anastassia N.;Roethlisberger, Daniela;Baker, David;Jorgensen, William L.
通讯作者：
Jorgensen, William L.
影响因子：
3.3
作者：
Antoniou, Dimitri;Schwartz, Steven D.
通讯作者：
Schwartz, Steven D.
影响因子：
3.3
作者：
Davarifar, Ardy;Antoniou, Dimitri;Schwartz, Steven D.
通讯作者：
Schwartz, Steven D.
影响因子：
3
作者：
BROOKS, BR;BRUCCOLERI, RE;KARPLUS, M
通讯作者：
KARPLUS, M
影响因子：
4.4
作者：
JORGENSEN, WL;CHANDRASEKHAR, J;KLEIN, ML
通讯作者：
KLEIN, ML