The mighty arginine, the stable quaternary amines, the powerful aromatics, and the aggressive phosphate: Their role in the noncovalent minuet
The mighty arginine, the stable quaternary amines, the powerful aromatics, and the aggressive phosphate: Their role in the noncovalent minuet
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DOI：
10.1021/pr034091l
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发表时间：
2004-05-01
影响因子：
4.4
通讯作者：
Woods, AS
中科院分区：
文献类型：
--
作者：
Woods, AS
在蛋白质组学时代，某些氨基酸残基和一些翻译后修饰在非共价复合物形成中的作用越来越重要，因为对生物分子之间相互作用的理解是结构功能关系难题的核心。在这项工作中，质谱被用来突出通过阳离子- π键的铵或胍-芳相互作用和通过盐桥形成的铵或胍-磷酸相互作用。这种相互作用是某些配体-受体相互作用和受体-受体相互作用的关键因素。此外，磷酸化残基和磷酸化脂质与胍和季铵形成非共价复合物的能力（主要通过库仑相互作用）得到证实，这可以解释某些膜包裹蛋白的稳定性，或者磷酸化在蛋白-蛋白相互作用中的可能作用。Dougherty的工作证明了蛋白质内部相互作用和折叠中的阳离子- π相互作用，本工作探索了肽间相互作用，即在含有相邻芳香残基的肽表位和含有相邻Arg的肽表位之间形成非共价复合物，作为更好地理解阳离子-pi复合物在蛋白质-蛋白质相互作用中的作用的模型。还研究了含芳香残基的多肽与季胺的配合物以及芳香化合物与精氨酸胍基的相互作用。考虑到大量的治疗性化合物含有芳香环和季胺，上述相互作用可能对更好地理解其作用机制具有重要意义。
In the age of proteomics, the role of certain amino acid residues and some post-translational modifications in noncovalent complex formation are gaining in importance, as the understanding of interactions between biological molecules, is at the heart of the structure function relationship puzzle. In this work, mass spectrometry is used to highlight ammonium- or guaniclinium-aromatic interactions through Cation-pi bonds and ammonium- or guanidinium-phosphate interactions through salt bridge formation. Such interactions are crucial factors in certain ligand-receptor interactions and receptor-receptor interactions. In addition, the ability of phosphorylated residues and phosphorylated lipids to form noncovalent complexes with guanidinium and quaternary ammonium (mostly through Coulombic interactions) is demonstrated, and could explain the stability Of Certain membrane embedded protein, or a possible role for phosphorylation in protein-protein interactions. Dougherty's work demonstrates cation-pi interactions in intra-protein interactions and folding, the present work explores inter-peptide interactions, i.e., the formation of noncovalent complexes between peptides' epitopes containing adjacent aromatic residues and ones containing adjacent Arg as a model to better understand the role of cation-pi complexes in protein-protein interaction. Complexes of peptides containing aromatic residues with quaternary amines as well as the interaction of aromatic compounds, with the guanidinium group of Arg are also investigated. Considering that an inordinate number of therapeutic compounds contain aromatic rings and quaternary amines, the above-described interactions could possibly be of great importance in better understanding their mechanism of action.