Fluoroalkyl and alkyl chains have similar hydrophobicities in binding to the "hydrophobic wall" of carbonic anhydrase.
Fluoroalkyl and alkyl chains have similar hydrophobicities in binding to the "hydrophobic wall" of carbonic anhydrase.
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DOI：
10.1021/ja2045293
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发表时间：
2011-09-07
影响因子：
15
通讯作者：
Whitesides, George M.
中科院分区：
文献类型：
--
作者：
Mecinovic, Jasmin;Snyder, Phillip W.;Mirica, Katherine A.;Bai, Serena;Mack, Eric T.;Kwant, Richard L.;Moustakas, Demetri T.;Heroux, Annie;Whitesides, George M.
疏水效应——非极性溶质在水中自由能量上有利的结合——对许多配体和蛋白质系统的结合起主要作用。本研究的目的是利用两种化学性质不同但结构相似的疏水性基团——脂肪族烃和脂肪族氟碳化合物——来研究疏水性在生物分子识别中的作用，并确定这两种基团的疏水性是否可以通过热力学和生物结构分析来区分。本文采用等温滴定量热法（ITC）研究了烷基链和氟烷基链对位取代的苯磺酰胺（H2NSO2C6H4-CONHCH2(CX2)nCX3, n = 0-4, X = H， F）与人碳酸酐酶II （HCA II）的结合热力学。烷基取代基和氟烷基取代基都有利于键合焓和键合熵的提高；这些贡献随着疏水取代基链长度的增加而增加。蛋白质-配体复合物的晶体学表明，所检查的所有配体的苯磺酰胺基团以相似的几何形状结合，尾部基团与HCA II的疏水壁（由残基Phe131， Val135， Pro202和Leu204的侧链组成）相关联，并且除了一个复合物（氟烷基系列中最长的成员）之外，蛋白质的结构对所有复合物都是难以区分的。结合热力学作为结构函数的分析与以下假设相一致：烷基链和氟烷基链与碳酸酐酶疏水表面的疏水结合主要是由于释放非最佳氢键水分子使HCA II的结合腔（包括疏水壁）水化，以及释放围绕配体疏水链的水分子。这项研究定义了在这个代表性的蛋白质和配体系统中，对疏水效应的焓和熵贡献的平衡：疏水相互作用，在这里，似乎包含了大约相等的焓（似乎来自水氢键分子之间加强的网络）和熵（来自水从构型限制的位置释放）的贡献。
The hydrophobic effect—the free-energetically favorable association of non-polar solutes in water—makes a dominant contribution to binding of many systems of ligands and proteins. The objective of this study was to examine the hydrophobic effect in biomolecular recognition using two chemically different, but structurally similar hydrophobic groups—aliphatic hydrocarbons and aliphatic fluorocarbons—and to determine whether the hydrophobicity of the two groups could be distinguished by thermodynamic and biostructural analysis. This paper uses isothermal titration calorimetry (ITC) to examine the thermodynamics of binding of benzenesulfonamides substituted in the para position with alkyl and fluoroalkyl chains (H2NSO2C6H4-CONHCH2(CX2)nCX3, n = 0–4, X = H, F) to human carbonic anhydrase II (HCA II). Both alkyl and fluoroalkyl substituents contribute favorably to the enthalpy and the entropy of binding; these contributions increase as the length of chain of the hydrophobic substituent increases. Crystallography of the protein-ligand complexes indicates that the benzenesulfonamide groups of all ligands examined bind with similar geometry, that the tail groups associate with the hydrophobic wall of HCA II (which is made up of the side chains of residues Phe131, Val135, Pro202, and Leu204), and that the structure of the protein is indistinguishable for all but one of the complexes (the longest member of the fluoroalkyl series). Analysis of the thermodynamics of binding as a function of structure is compatible with the hypothesis that hydrophobic binding of both alkyl and fluoroalkyl chains to hydrophobic surface of carbonic anhydrase is due primarily to the release of non-optimally hydrogen-bonded water molecules that hydrate the binding cavity (including the hydrophobic wall) of HCA II and to the release of water molecules that surround the hydrophobic chain of the ligands. This study defines the balance of enthalpic and entropic contributions to the hydrophobic effect in this representative system of protein and ligand: hydrophobic interactions, here, seem to comprise approximately equal contributions from enthalpy (plausibly from strengthening networks among molecules of water hydrogen bonds) and entropy (from release of water from configurationally restricted positions).
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影响因子：
7.3
作者：
GAO, JM;QIAO, S;WHITESIDES, GM
通讯作者：
WHITESIDES, GM
影响因子：
4.1
作者：
Krishnamurthy, Vijay M.;Bohall, Brooks R.;Whitesides, George M.
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Whitesides, George M.
影响因子：
64.8
作者：
Cheng, YK;Rossky, PJ
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Rossky, PJ
影响因子：
64.8
作者：
Liu, P;Huang, XH;Berne, BJ
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Berne, BJ
影响因子：
15
作者：
Malham, R;Johnstone, S;Homans, SW
通讯作者：
Homans, SW