Japan Synchrotron Radiation Research Institute (SPring-8), 1-1-1 Kouto, Sayo, Hyogo 679-5198, Japan.
Protein Eng Des Sel. 2011 Mar;24(3):269-74. doi: 10.1093/protein/gzq101. Epub 2010 Nov 17.
While biotechnological applications of arginine (Arg) as a solution additive that prevents protein aggregation are increasing, the molecular mechanism of its effects remains unclear. In this study, we investigated the Arg-lysozyme complex by high-resolution crystallographic analysis. Three Arg molecules were observed to be in close proximity to aromatic amino acid residues of the protein surface, and their occupancies gradually increased with increasing Arg concentration. These interactions were mediated by electrostatic, hydrophobic and cation-π interactions with the surface residues. The binding of Arg decreased the accessible surface area of aromatic residues by 40%, but increased that of charged residues by 10%. These changes might prevent intermolecular hydrophobic interactions by shielding hydrophobic regions of the lysozyme surface, resulting in an increase in protein solubility.
虽然精氨酸 (Arg) 作为一种防止蛋白质聚集的溶液添加剂在生物技术中的应用越来越多，但它的作用机制仍不清楚。在这项研究中，我们通过高分辨率晶体学分析研究了 Arg-溶菌酶复合物。观察到三个 Arg 分子与蛋白质表面的芳香族氨基酸残基接近，并且随着 Arg 浓度的增加，它们的占有率逐渐增加。这些相互作用是通过静电、疏水和阳离子-π 相互作用与表面残基介导的。Arg 的结合使芳香族残基的可及表面积减少了 40%，但使带电荷残基的可及表面积增加了 10%。这些变化可能通过屏蔽溶菌酶表面的疏水区域来防止分子间的疏水相互作用，从而增加蛋白质的溶解度。
