Molecular Basis of Aqueous-like Activity of Lipase Treated with Glucose-Headed Surfactant in Organic Solvent.
Molecular Basis of Aqueous-like Activity of Lipase Treated with Glucose-Headed Surfactant in Organic Solvent.
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有机溶剂中葡萄糖头表面活性剂处理脂肪酶类水活性的分子基础。
DOI：
10.1021/acs.jpcb.8b07686
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Im,Wonpil
中科院分区：
文献类型：
--
作者：
Lee,HuiSun;Oh,Yeonock;Kim,Mahn-Joo;Im,Wonpil
脂肪酶可用作催化剂，特别是用于外消旋醇和酯的动力学拆分。然而，它们在有机介质中的活性较差，限制了它们的工业应用。我们最近发现，伯克霍尔德氏菌的脂蛋白脂肪酶在有机溶剂中，如果用葡萄糖头表面活性剂（GHS）包被蛋白质，则该蛋白质显示出显著增强的活性。在这里，我们调查的分子基础，这种增强酶活性在有机溶剂中进行分子动力学模拟onBurkholderia头孢菌素酶作为一种模型酶。模拟结果表明，脂肪酶活性的提高源于GHS在水和有机溶剂中的双重作用。GHS分子通过在水中提供围绕活性位点的脂质样微环境来维持脂肪酶的开放构象，并且通过在有机溶剂中提供围绕脂肪酶表面的水样微环境来稳定其天然活性构象。我们的数据还表明，有机助溶剂的作用，可以促进封闭到开放的构象变化，在冷冻干燥过程中。本研究的计算方法为设计更有效的表面活性剂分子以提高脂肪酶在有机溶剂中的活性奠定了基础。
Lipases are useful as catalysts, particularly for the kinetic resolution of racemic alcohols and esters. However, their industrial applications are limited by their poor activities in organic media. We recently found that a lipoprotein lipase fromBurkholderiaspecies displays dramatically enhanced activity in organic solvent if the protein is coated with glucose-headed surfactant (GHS). Here we investigate the molecular basis of this enhanced enzymatic activity in organic solvent by performing molecular dynamics simulations onBurkholderia cepacialipase as a model enzyme. Our simulation results indicate that the enhanced activity of lipase stems from a dual function of GHSs different in water and organic solvent. GHS molecules maintain the open conformation of lipase by providing lipid-like microenvironment surrounding the active site in water and stabilize its native active conformation by providing water-like microenvironment around the surface of the lipase in the organic solvent. Our data also suggest the role of organic cosolvent that can facilitate closed-to-open conformational changes during the freeze-drying process. The computational approach in this study lays its potential for guiding the design of more effective surfactant molecules to improve the activity of lipases in organic solvent.