Quantifying Interactions of Nucleobase Atoms with Model Compounds for the Peptide Backbone and Glutamine and Asparagine Side Chains in Water
Quantifying Interactions of Nucleobase Atoms with Model Compounds for the Peptide Backbone and Glutamine and Asparagine Side Chains in Water
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DOI：
10.1021/acs.biochem.8b00087
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发表时间：
2018-04-17
期刊：
影响因子：
2.9
通讯作者：
Record, M. Thomas, Jr.
中科院分区：
文献类型：
--
作者：
Cheng, Xian;Shkel, Irina A.;Record, M. Thomas, Jr.
烷基脲显示烃和酰胺基团，蛋白质的主要官能团。为了获得所需的热力学信息，分析酰胺和蛋白质与核碱基和核酸的相互作用，我们量化的优先相互作用的烷基脲与核碱基不同的量和组成的水可及表面积（阿萨）的溶解度测定。使用已建立的基于添加剂ASA的分析，我们解释这些热力学结果，以确定每个烷基脲与五种类型的核碱基统一原子（羰基sp（2）O，氨基sp（3）N，环sp（2）N，甲基sp（3）C和环sp（2）C）的相互作用。所有烷基脲都与核碱基sp（2）C和sp（3）C原子有利地相互作用;这些相互作用随着脲的烷基化水平的增加而变得更有利。与核碱基sp（2）O的相互作用对脲最有利，对甲基脲和乙基脲不太有利，对二烷基脲不利。与每种核碱基原子类型的相互作用对总体烷基脲-核碱基相互作用的贡献与该原子类型的阿萨成比例，具有比例常数（相互作用强度）α，如先前对脲观察到的。烷基脲与核碱基原子类型相互作用的α值趋势与相应酰胺化合物原子类型的α值趋势平行，因为核碱基α值更有利而抵消。乙基化和甲基化脲的比较表明酰胺化合物sp（3）C与核碱基sp（2）C、sp（3）C、sp（2）N和sp（3）N原子的相互作用是有利的，而酰胺sp（3）C-核碱基sp（2）O相互作用是不利的。尿素与核碱基sp（2）O的强有利相互作用和与核碱基sp（3）N的弱有利相互作用表明酰胺sp（2）N-核碱基sp（2）O和核碱基sp（3）N-酰胺sp（2）O氢键（NH中心点中心点O=C）相互作用是有利的，而酰胺sp（2）N-核碱基sp（3）N相互作用是不利的。这些有利的酰胺-核碱基氢键相互作用普遍存在于特定的蛋白质-核苷酸复合物中。
Alkylureas display hydrocarbon and amide groups, the primary functional groups of proteins. To obtain the thermodynamic information that is needed to analyze interactions of amides and proteins with nucleobases and nucleic acids, we quantify preferential interactions of alkylureas with nucleobases differing in the amount and composition of water-accessible surface area (ASA) by solubility assays. Using an established additive ASA-based analysis, we interpret these thermodynamic results to determine interactions of each alkylurea with five types of nucleobase unified atoms (carbonyl sp(2)O, amino sp(3)N, ring sp(2)N, methyl sp(3)C, and ring sp(2)C). All alkylureas interact favorably with nucleobase sp(2)C and sp(3)C atoms; these interactions become more favorable with an increasing level of alkylation of urea. Interactions with nucleobase sp(2)O are most favorable for urea, less favorable for methylurea and ethylurea, and unfavorable for dialkylated ureas. Contributions to overall alkylurea-nucleobase interactions from interactions with each nucleobase atom type are proportional to the ASA of that atom type with proportionality constant (interaction strength) alpha, as observed previously for urea. Trends in alpha-values for interactions of alkylureas with nucleobase atom types parallel those for corresponding amide compound atom types, offset because nucleobase alpha-values are more favorable. Comparisons between ethylated and methylated ureas show interactions of amide compound sp(3)C with nucleobase sp(2)C, sp(3)C, sp(2)N, and sp(3)N atoms are favorable while amide sp(3)C-nucleobase sp(2)O interactions are unfavorable. Strongly favorable interactions of urea with nucleobase sp(2)O but weakly favorable interactions with nucleobase sp(3)N indicate that amide sp(2)N-nucleobase sp(2)O and nucleobase sp(3)N-amide sp(2)O hydrogen bonding (NH center dot center dot center dot O=C) interactions are favorable while amide sp(2)N-nucleobase sp(3)N interactions are unfavorable. These favorable amide-nucleobase hydrogen bonding interactions are prevalent in specific protein-nucleotide complexes.