Insight Derived from Molecular Dynamics Simulation into Substrate-Induced Changes in Protein Motions of Proteinase K
Insight Derived from Molecular Dynamics Simulation into Substrate-Induced Changes in Protein Motions of Proteinase K
复制标题
通过分子动力学模拟深入了解底物诱导的蛋白酶 K 蛋白质运动变化
DOI：
10.1080/073911010010524953
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发表时间：
2010-10
影响因子：
4.4
通讯作者：
Tao, Yan
中科院分区：
文献类型：
--
作者：
Liu, Shu-Qun;Rao, Zi-He;Tao, Yan
摘要由于丝氨酸蛋白酶K在工业、农业和生物技术上的重要性，人们利用X射线晶体学、定点突变和动力学测量等实验方法对其进行了广泛的研究。然而，酶机制的细节方面，如底物结合，释放和相关的调控仍然没有研究。采用分子动力学（MD）方法模拟了蛋白酶K单独和与肽底物AAPA复合时的动力学和分子运动，研究了底物结合对蛋白酶K动力学和分子运动的影响。结果表明，在模拟过程中，底物复合的蛋白酶K采取更紧凑和稳定的构象比无底物的形式。进一步的基本动力学（艾德）分析表明，主要的内部运动被限制在一个非常小的维度的子空间。在底物结合时，蛋白酶的整体柔性降低;并且不仅在底物结合区域中而且在与底物结合凹槽/口袋相对的区域中观察到明显的位移。由大协调运动引起的动态口袋被认为与底物识别、结合、定向和产物释放有关;结合凹槽/口袋对面区域的显著位移被认为在调节酶-底物相互作用的动力学中起作用。我们的模拟结果补充了生化和结构研究，突出了蛋白酶K功能特性的动力学机制。
Abstract Because of the significant industrial, agricultural and biotechnological importance of serine protease proteinase K, it has been extensively investigated using experimental approaches such as X-ray crystallography, site-directed mutagenesis and kinetic measurement. However, detailed aspects of enzymatic mechanism such as substrate binding, release and relevant regulation remain unstudied. Molecular dynamics (MD) simulations of the proteinase K alone and in complex with the peptide substrate AAPA were performed to investigate the effect of substrate binding on the dynamics/molecular motions of proteinase K. The results indicate that during simulations the substrate-complexed proteinase K adopt a more compact and stable conformation than the substrate-free form. Further essential dynamics (ED) analysis reveals that the major internal motions are confined within a subspace of very small dimension. Upon substrate binding, the overall flexibility of the protease is reduced; and the noticeable displacements are observed not only in substrate-binding regions but also in regions opposite the substrate-binding groove/pockets. The dynamic pockets caused by the large concerted motions are proposed to be linked to the substrate recognition, binding, orientation and product release; and the significant displacements in regions opposite the binding groove/pockets are considered to play a role in modulating the dynamics of enzyme-substrate interaction. Our simulation results complement the biochemical and structural studies, highlighting the dynamic mechanism of the functional properties of proteinase K.
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影响因子：
5.6
作者：
David W. Miller;D. Agard
通讯作者：
David W. Miller;D. Agard
DOI：
10.1080/07391102.2008.10507236
发表时间：
2008-10
影响因子：
4.4
作者：
U. Sonavane;Sai Kumar Ramadugu;R. Joshi
通讯作者：
U. Sonavane;Sai Kumar Ramadugu;R. Joshi
DOI：
10.1002/(sici)1097-0134(19980501)31:2
发表时间：
1998-05
期刊：
Proteins: Structure
影响因子：
--
作者：
Qin Zou;Susan M. Habermann‐Rottinghaus;K. Murphy
通讯作者：
Qin Zou;Susan M. Habermann‐Rottinghaus;K. Murphy
DOI：
10.1093/protein/10.2.149
发表时间：
1997-02-01
期刊：
PROTEIN ENGINEERING
影响因子：
--
作者：
Peters, GH;vanAalten, DMF;Bywater, R
通讯作者：
Bywater, R
影响因子：
2.4
作者：
Hess, B
通讯作者：
Hess, B