Comparison of entropic contributions to binding in a "hydrophilic" versus "hydrophobic" ligand-protein interaction.
Comparison of entropic contributions to binding in a "hydrophilic" versus "hydrophobic" ligand-protein interaction.
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DOI：
10.1021/ja101362u
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发表时间：
2010-06-30
影响因子：
15
通讯作者：
Homans SW
中科院分区：
文献类型：
--
作者：
Syme NR;Dennis C;Bronowska A;Paesen GC;Homans SW
在本研究中，我们的特点组胺结合重组组胺结合蛋白（rRaHBP 2），从棕耳蜱Rhipicephalus approxulatus分离的脂质运载蛋白家族的成员的热力学。该蛋白的结合口袋含有许多带电残基，与组胺结合一致，因此是“亲水性”结合剂的典型实例。相比之下，脂质运载蛋白家族的第二个成员，重组主要尿蛋白（rMUP），结合小的疏水配体，与rRaHBP 2相比，具有相似的总结合熵。在广泛研究了配体结合热力学rMUP以前，我们在本研究中获得的数据HBP使这些经典的不同的结合过程中的熵的贡献，从配体，蛋白质和溶剂的结合驱动力的比较。在rRaHBP 2的情况下，我们发现配体去溶剂化对结合有有利的熵贡献;然而，由于配体自由度的丧失以及溶剂水分子的螯合而产生的主要不利贡献，结合的总体熵是不利的。进入复合物中的结合口袋。这与rMUP中的结合形成对比，在rMUP中，蛋白结合口袋的去溶剂化对结合的总熵的贡献较小，因为口袋在结合之前基本上去溶剂化。
In the present study we characterize the thermodynamics of binding of histamine to recombinant histamine-binding protein (rRaHBP2), a member of the lipocalin family isolated from the brown-ear tick Rhipicephalus appendiculatus. The binding pocket of this protein contains a number of charged residues, consistent with histamine binding, and is thus a typical example of a “hydrophilic” binder. In contrast, a second member of the lipocalin family, the recombinant major urinary protein (rMUP), binds small hydrophobic ligands, with a similar overall entropy of binding in comparison with rRaHBP2. Having extensively studied ligand binding thermodynamics for rMUP previously, the data we obtained in the present study for HBP enables a comparison of the driving forces for binding between these classically distinct binding processes in terms of entropic contributions from ligand, protein, and solvent. In the case of rRaHBP2, we find favorable entropic contributions to binding from desolvation of the ligand; however, the overall entropy of binding is unfavorable due to a dominant unfavorable contribution arising from the loss of ligand degrees of freedom, together with the sequestration of solvent water molecules into the binding pocket in the complex. This contrasts with binding in rMUP where desolvation of the protein binding pocket makes a minor contribution to the overall entropy of binding given that the pocket is substantially desolvated prior to binding.
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影响因子：
2.7
作者：
d'Auvergne EJ;Gooley PR
通讯作者：
Gooley PR
影响因子：
2.7
作者：
d'Auvergne EJ;Gooley PR
通讯作者：
Gooley PR
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
DOI：
10.1039/p29930000799
发表时间：
1993-05-01
期刊：
JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 2
影响因子：
--
作者：
KLAMT, A;SCHUURMANN, G
通讯作者：
SCHUURMANN, G
影响因子：
2.2
作者：
de la Torre, JG;Huertas, ML;Carrasco, B
通讯作者：
Carrasco, B