Jha Indrani, Attri Pankaj, Venkatesu Pannuru
Department of Chemistry, University of Delhi, Delhi - 110007, India.
Phys Chem Chem Phys. 2014 Mar 28;16(12):5514-26. doi: 10.1039/c3cp54398f. Epub 2014 Feb 5.
The nature of solvent-biomolecule interactions is generally weak and non-specific. The addition of ionic liquids (ILs), which have emerged as a new class of solvents, strengthen the stability of some proteins whereas the same ILs weaken the stability of some other proteins. Although ILs are commonly used for the stabilization of biomolecules, the bimolecular interactions of their stabilization-destabilization is still an active subject of considerable interest and studies on this topic have been limited. To reveal the impact of ILs on the stability of proteins, a series of protic ILs possessing a tetra-alkyl ammonium cation R4N with a hydroxide OH anion were synthesized. In this study, we report the structural stability of heme proteins such as myoglobin (Mb) and hemoglobin (Hb) in a series of ammonium-based ILs such as tetramethyl ammonium hydroxide (CH3)4NOH (TMAH), tetraethyl ammonium hydroxide (C2H5)4NOH (TEAH), tetrapropyl ammonium hydroxide (C3H7)4NOH (TPAH) and tetrabutyl ammonium hydroxide (C4H9)4NOH (TBAH) by fluorescence and circular dichroism (CD) spectroscopic studies. Our experimental results reveal that less viscous ILs carrying smaller alkyl chain such as TMAH are strong destabilizers of the heme proteins as compared to the ILs carrying bulkier alkyl chains which are more viscous ILs, such as TBAH. Therefore, our results demonstrate that the addition of these ILs to the heme proteins decreases their thermal stability allowing the protein to be in an unfolded state at lower temperatures. Further, we describe the molecular-structural interaction of the heme proteins with the ILs (molecule like a ligand) by the PatchDocking method.
溶剂与生物分子之间的相互作用通常较弱且不具有特异性。离子液体（ILs）作为一类新型溶剂出现后，添加离子液体可增强某些蛋白质的稳定性，而同样的离子液体却会削弱另一些蛋白质的稳定性。尽管离子液体常用于生物分子的稳定化，但它们在稳定 - 去稳定方面的双分子相互作用仍是一个备受关注的活跃课题，对此主题的研究一直有限。为揭示离子液体对蛋白质稳定性的影响，合成了一系列具有四烷基铵阳离子R4N和氢氧根OH阴离子的质子型离子液体。在本研究中，我们通过荧光和圆二色性（CD）光谱研究报告了血红素蛋白如肌红蛋白（Mb）和血红蛋白（Hb）在一系列铵基离子液体中的结构稳定性，这些铵基离子液体包括氢氧化四甲铵(CH3)4NOH（TMAH）、氢氧化四乙铵(C2H5)4NOH（TEAH）、氢氧化四丙铵(C3H7)4NOH（TPAH）和氢氧化四丁铵(C4H9)4NOH（TBAH）。我们的实验结果表明，与携带较大烷基链且更具粘性的离子液体（如TBAH）相比，携带较小烷基链且粘性较小的离子液体（如TMAH）是血红素蛋白的强去稳定剂。因此，我们的结果表明，向血红素蛋白中添加这些离子液体会降低其热稳定性，使蛋白质在较低温度下处于未折叠状态。此外，我们通过PatchDocking方法描述了血红素蛋白与离子液体（类似配体的分子）的分子结构相互作用。
