NMR spectroscopic investigation of ψ torsion angle distribution in unfolded ubiquitin from analysis of 3J(Cα,Cα) coupling constants and cross-correlated ΓcHNN,CαHα relaxation rates
NMR spectroscopic investigation of ψ torsion angle distribution in unfolded ubiquitin from analysis of 3J(Cα,Cα) coupling constants and cross-correlated ΓcHNN,CαHα relaxation rates
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DOI：
10.1021/ja001390s
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发表时间：
2000-12-06
影响因子：
15
通讯作者：
Schwalbe, H
中科院分区：
文献类型：
--
作者：
Peti, W;Hennig, M;Schwalbe, H
蛋白质的变性状态由一系列的构象组成。统计模型已经被开发出来，用来描述肽和蛋白质这种动态状态的构象平均过程。我们的模型2,3假设在高浓度变性剂（如8 M尿素）下研究的多肽链中的所有相互作用都是局部的。此外，通过统计分析非二级结构元件的天然折叠蛋白数据库中残基的扭转角分布，可以描述构象的分布。所有氨基酸的Ramachandran图（图1）表明，φ采样主要局限于-60> φ>-180，而ψ采样涵盖了图中的ψ≈-30和100< ψ< 180。异核磁共振波谱是验证基于我们模型的预测的关键。核磁共振研究表明，从蛋白质数据库中获得的预测结果与φ6和14角周围旋转体分布的氨基酸特异性变化之间存在显著的相关性，对于在pH为2的8 M尿素中变性的蛋白质溶菌酶，以及对小的非结构化肽的研究。7
The denatured state of a protein consists of an ensemble of conformers. Statistical models have been developed to describe the conformational averaging process for this dynamic state of peptides1 and proteins. 2, 3 Our model2, 3 assumes that all the interactions in a polypeptide chain studied at high concentrations of denaturant such as 8 M urea are local. Moreover, the distribution of conformers can be described by a statistical analysis of the distribution of torsion angles of residues in a database of native folded proteins not located in secondary structure elements. The Ramachandran diagram for all amino acids (Figure 1) shows that φ sampling is mainly restricted to values-60> φ>-180, while ψ sampling covers ψ≈-30 and 100< ψ< 180 of the diagram.Heteronuclear NMR spectroscopy has been key to validate predictions based on our model. NMR studies revealed a remarkable correlation between predictions taken from the protein database and amino acid specific variations of the rotamer distribution around the angles φ6 and 1 4 for the protein lysozyme denatured in 8 M urea at pH 2 as well as in studies of small unstructured peptides. 7