Insights into lid movements of Burkholderia cepacia lipase inferred from molecular dynamics simulations
Insights into lid movements of Burkholderia cepacia lipase inferred from molecular dynamics simulations
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DOI：
10.1002/prot.22462
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发表时间：
2009-11-15
影响因子：
2.9
通讯作者：
Andre, Isabelle
中科院分区：
文献类型：
--
作者：
Barbe, Sophie;Lafaquiere, Vincent;Andre, Isabelle
许多脂肪酶在水/脂界面上的界面活化是由覆盖酶活性位点的所谓盖子结构域的大的构象变化介导的。在这里，我们研究了使用分子动力学模拟在不同的显式溶剂环境（水，辛烷和水/辛烷界面）的分子机制，盖运动洋葱伯克霍尔德菌脂肪酶可能运作。虽然B.洋葱脂肪酶迄今为止仅以开放构象结晶，该研究首次揭示了该酶在溶剂的影响下经历的主要构象重排，溶剂使活性位点暴露或屏蔽底物。在水介质中，盖子从打开到关闭的构象，而相反的运动发生在有机环境中。特别是，一个子域的作用面临的盖子上B。洋葱脂肪酶的构象重排进行了研究，使用位置限制的MD模拟。我们的结论表明，B的α 9螺旋侧链的唯一移动性。洋葱脂肪酶是完全完成盖构象变化所必需的，所述盖构象变化基本上由α 5螺旋运动驱动。进一步检查了所选择的α 5疏水残基对眼睑运动的作用。两个残基V138和F142的计算机突变显示出显著改变了B的构象行为。洋葱脂肪酶总体而言，我们的研究结果提供了宝贵的洞察所发挥的作用，周围环境的盖子构象重排和激活的B。洋葱脂肪酶Proteins 2009; 77：509-523. (C)2009 Wiley-Liss，Inc.
The interfacial activation of many lipases at water/lipid interface is mediated by large conformational changes of a so-called lid subdomain that covers up the enzyme active site. Here we investigated using molecular dynamic simulations in different explicit solvent environments (water, octane and water/octane interface) the molecular mechanism by which the lid motion of Burkholderia cepacia lipase might operate. Although B. cepacia lipase has so far only been crystallized in open conformation, this study reveals for the first time the major conformational rearrangements that the enzyme undergoes under the influence of the solvent, which either exposes or shields the active site from the substrate. In aqueous media, the lid switches from an open to a closed conformation while the reverse motion occurs in organic environment. In particular, the role of a subdomain facing the lid on B. cepacia lipase conformational rearrangements was investigated using position-restrained MD simulations. Our conclusions indicate that the sole mobility of alpha 9 helix side-chains of B. cepacia lipase is required for the full completion of the lid conformational change which is essentially driven by alpha 5 helix movement. The role of selected alpha 5 hydrophobic residues on the lid movement was further examined. In silico mutations of two residues, V138 and F142, were shown to drastically modify the conformational behavior of B. cepacia lipase. Overall, our results provide valuable insight into the role played by the surrounding environment on the lid conformational rearrangement and the activation of B. cepacia lipase. Proteins 2009; 77:509-523. (C) 2009 Wiley-Liss, Inc.