Structural basis of neurophysin hormone specificity: Geometry, polarity, and polarizability in aromatic ring interactions.
Structural basis of neurophysin hormone specificity: Geometry, polarity, and polarizability in aromatic ring interactions.
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神经素激素特异性的结构基础：芳香环相互作用中的几何、极性和极化性。
DOI：
10.1110/ps.8.4.820
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Haschemeyer,RH
中科院分区：
文献类型：
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作者：
Breslow,E;Mombouyran,V;Deeb,R;Zheng,C;Rose,JP;Wang,BC;Haschemeyer,RH
通过分析配体neurophysin晶体结构背景下一系列肽的结合，探索了neurophysin结合位点对肽位置2中芳香残基的特异性的结构起源。一种新的描述结合位点的货车德瓦耳斯表面的建模方法辅助分析。特别注意的是异常大的（5千卡/摩尔）之间的Phe和Leu在位置2的结合自由能的差异，值代表超过三倍的最大预期的基础上的疏水性单独，另外显着，因为建模表明，Leu侧链很容易容纳的结合口袋。尽管获得了残基2侧链和肽α-氨基的结合相互作用之间弱热力学联系的证据，但认为两个因素是核心因素。(1)结合的Leu侧链只能建立Phe侧链可用的货车范德华接触的三分之一。(2)结合的Phe侧链似乎通过与结合口袋中的非芳族极性和硫配体的更有利的偶极和诱导偶极相互作用而相对于Leu另外稳定，如通过检查其在口袋中的相互作用，分析Phe和Leu侧链从水转移到其它相的详细能量学，并与该体系中残基1侧链结合的热力学和结构数据进行比较。虽然这种极性相互作用的芳香环以前已经观察到，目前的结果表明，它们的潜在的显着的热力学贡献的蛋白质结构和配体识别。
The structural origins of the specificity of the neurophysin hormone-binding site for an aromatic residue in peptide position 2 were explored by analyzing the binding of a series of peptides in the context of the crystal structure of liganded neurophysin. A new modeling method for describing the van der Waals surface of binding sites assisted in the analysis. Particular attention was paid to the unusually large (5 kcal/mol) difference in binding free energy between Phe and Leu in position 2, a value representing more than three times the maximum expected based on hydrophobicity alone, and additionally remarkable since modeling indicated that the Leu side chain was readily accommodated by the binding pocket. Although evidence was obtained of a weak thermodynamic linkage between the binding interactions of the residue 2 side chain and of the peptide α-amino group, two factors are considered central. (1) The bound Leu side chain can establish only one-third of the van der Waals contacts available to a Phe side chain. (2) The bound Phe side chain appears to be additionally stabilized relative to Leu by more favorable dipole and induced dipole interactions with nonaromatic polar and sulfur ligands in the binding pocket, as evidenced by examination of its interactions in the pocket, analysis of the detailed energetics of transfer of Phe and Leu side chains from water to other phases, and comparison with thermodynamic and structural data for the binding of residue 1 side chains in this system. While such polar interactions of aromatic rings have been previously observed, the present results suggest their potential for significant thermodynamic contributions to protein structure and ligand recognition.