Flexibility and enzymatic cold-adaptation: A comparative molecular dynamics investigation of the elastase family
Flexibility and enzymatic cold-adaptation: A comparative molecular dynamics investigation of the elastase family
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DOI：
10.1016/j.bbapap.2006.06.005
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发表时间：
2006-08-01
影响因子：
3.2
通讯作者：
De Gioia, Luca
中科院分区：
文献类型：
--
作者：
Papaleo, Elena;Riccardi, Laura;De Gioia, Luca
在不同温度下对具有代表性的中温和亲冷弹性酶进行了分子动力学模拟，以探索特定酶家族内部冷适应的分子基础。本文从二级结构、分子柔韧性、分子内和蛋白质-溶剂相互作用等方面对亲冷弹性蛋白酶的分子动力学轨迹进行了比较和分析，揭示了亲冷弹性蛋白酶在低温下高效催化活性的分子特征。比较分子动力学研究表明，调节蛋白质-溶剂相互作用的数量并不是亲心理弹性酶在低温下提高催化活性的进化策略。此外，形成催化三联体和特异性口袋的残基的柔韧性和溶剂可及性在冷适应酶和热适应酶中是相当的。相反，在两种酶中具有不同氨基酸组成的环区，聚集在活性位点或特异性口袋周围，在冷适应酶中具有增强的灵活性。值得注意的是，与中温弹性酶相比，亲心弹性酶在远离功能位点的一些分散区域具有较低的柔韧性，这与假设一致，即远离功能位点区域的局部刚性有利于亲心酶的催化活性。(c) 2006 Elsevier B.V.版权所有
Molecular dynamics simulations of representative mesophilic and psycrophilic elastases have been carried out at different temperatures to explore the molecular basis of cold adaptation inside a specific enzymatic family. The molecular dynamics trajectories have been compared and analyzed in terms of secondary structure, molecular flexibility, intramolecular and protein-solvent interactions, unravelling molecular features relevant to rationalize the efficient catalytic activity of psychrophilic elastases at low temperature. The comparative molecular dynamics investigation reveals that modulation of the number of protein-solvent interactions is not the evolutionary strategy followed by the psycrophilic elastase to enhance catalytic activity at low temperature. In addition, flexibility and solvent accessibility of the residues forming the catalytic triad and the specificity pocket are comparable in the cold- and warm-adapted enzymes. Instead, loop regions with different amino acid composition in the two enzymes, and clustered around the active site or the specificity pocket, are characterized by enhanced flexibility in the cold-adapted enzyme. Remarkably, the psycrophilic elastase is characterized by reduced flexibility, when compared to the mesophilic counterpart, in some scattered regions distant from the functional sites, in agreement with hypothesis suggesting that local rigidity in regions far from functional sites can be beneficial for the catalytic activity of psychrophilic enzymes. (c) 2006 Elsevier B.V. All rights reserved.