Dynamic allostery can drive cold adaptation in enzymes.
Dynamic allostery can drive cold adaptation in enzymes.
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DOI：
10.1038/s41586-018-0183-2
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发表时间：
2018-06
期刊：
影响因子：
64.8
通讯作者：
Hilser VJ
中科院分区：
文献类型：
--
作者：
Saavedra HG;Wrabl JO;Anderson JA;Li J;Hilser VJ
生物对环境生态位的适应是进化的标志。一个普遍的例子是热适应，其中两个后代在不同的极端温度下进化。这些生物体之间的生理差异是催化基本反应的酶的变化，来自每个生物体的直系同源物经历适应性突变，在各自的生理温度下保持相似的催化速率。然而，负责这些适应性差异的序列变化通常位于远离底物结合位点的表面暴露位点，使酶的活性位点在结构上不受干扰。这种变化如何通过变构传播到活性位点来调节活性尚不清楚。在这里，我们表明，熵调谐的变化，可以工程到大肠杆菌腺苷酸激酶（AK）的远端网站，以定量评估的作用，确定亲和力，营业额，并在驱动适应的作用的动态。这些结果不仅揭示了基于动力学的变构调节机制，而且揭示了关键酶参数控制的空间分离。一个移动的结构域（即LID）中的波动控制底物亲和力，而另一个结构域（即AMPbd）中的动态衰减影响控制酶周转的限速构象变化。因此，基于动力学的调节可能代表了一种优雅的、广泛的、以前未实现的进化适应机制，它在不改变基态结构的情况下微调生物功能。此外，由于刚体构象变化在这两个领域被认为是限制营业额的速率，这些适应研究揭示了一个新的范式，了解动态和营业额之间的关系在AK。
Adaptation of organisms to environmental niches is a hallmark of evolution. One prevalent example is that of thermal adaptation, wherein two descendants evolve at different temperature extremes. Underlying the physiological differences between such organisms are changes in enzymes catalyzing essential reactions, with orthologues from each organism undergoing adaptive mutations that preserve similar catalytic rates at their respective physiological temperatures . The sequence changes responsible for these adaptive differences, however, are often at surface exposed sites distant from the substrate binding site, leaving the active site of the enzyme structurally unperturbed. How such changes are allosterically propagated to the active site, to modulate activity, is not known. Here we show that entropy-tuning changes can be engineered into distal sites of Escherichia coli adenylate kinase (AK) to quantitatively assess the role of dynamics in determining affinity, turnover, and the role in driving adaptation. The results not only reveal a dynamics-based allosteric tuning mechanism, but also uncover a spatial separation of the control of key enzymatic parameters. Fluctuations in one mobile domain (i.e. the LID) control substrate affinity, while dynamic attenuation in the other (i.e. the AMPbd) affects rate-limiting conformational changes governing enzyme turnover. Dynamics-based regulation may thus represent an elegant, widespread, and previously unrealized evolutionary adaptation mechanism that fine-tunes biological function without altering the ground state structure. Furthermore, because rigid-body conformational changes in both domains were thought to be rate limiting for turnover, these adaptation studies reveal a new paradigm for understanding the relationship between dynamics and turnover in AK.
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影响因子：
4.4
作者：
Eyring, H
通讯作者：
Eyring, H
影响因子：
3.3
作者：
Hansen, D. Flemming;Vallurupalli, Pramodh;Kay, Lewis E.
通讯作者：
Kay, Lewis E.
DOI：
10.1073/pnas.95.19.11476
发表时间：
1998-09-15
影响因子：
11.1
作者：
Fields, PA;Somero, GN
通讯作者：
Somero, GN
影响因子：
3.4
作者：
Rogne, Per;Wolf-Watz, Magnus
通讯作者：
Wolf-Watz, Magnus
DOI：
10.1002/prot.1
发表时间：
1996-06-01
期刊：
PROTEINS-STRUCTURE FUNCTION AND GENETICS
影响因子：
--
作者：
DAquino, JA;Gomez, J;Freire, E
通讯作者：
Freire, E