CHARACTERIZATION OF TERTIARY INTERACTIONS IN A FOLDED PROTEIN BY NMR METHODS - STUDIES OF PH-INDUCED STRUCTURAL-CHANGES IN HUMAN GROWTH-HORMONE
CHARACTERIZATION OF TERTIARY INTERACTIONS IN A FOLDED PROTEIN BY NMR METHODS - STUDIES OF PH-INDUCED STRUCTURAL-CHANGES IN HUMAN GROWTH-HORMONE
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DOI：
10.1021/bi00151a028
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发表时间：
1992-09-15
期刊：
影响因子：
2.9
通讯作者：
DALBOGE, H
中科院分区：
文献类型：
--
作者：
ABILDGAARD, F;JORGENSEN, AMM;DALBOGE, H
研究了pH诱导的人生长激素（hGH）的构象变化，使用一种新的定量NMR方法，该方法将C-13标记的特定骨架羰基碳与相应的C-13共振的完整光谱分析相结合。因此，对hGH的26个Leu残基的羰基共振及其随pH的变化的完整分析提供了有关蛋白质平衡折叠过程的详细信息，包括有关折叠动力学的信息。通过结合这一信息与pH值的依赖性容易识别的H-1共振，在羰基碳光谱中观察到的pH值引起的变化可以与蛋白质中的特定区域相关联，并可以归因于一系列的局部调整的三级结构，在球状折叠蛋白质中的不同残基之间的氢键相互作用或静电相互作用的变化所带来的。这些调整的交换前生命周期范围从几分之一毫秒到几毫秒。
The pH-induced conformational changes in human growth hormone (hGH) have been studied, using a new quantitative NMR approach that combines C-13 labeling of specific backbone carbonyl carbons with a complete spectral analysis of the corresponding C-13 resonances. Thus, a complete analysis of the carbonyl resonances of the 26 Leu residues of hGH and their variation with pH provided detailed information about the equilibrium folding processes of the protein, including information about the kinetics of the folding. By combining this information with the pH dependence of readily identifiable H-1 resonances, the pH-induced changes observed in the carbonyl carbon spectra can be associated with specific regions in the protein and can be ascribed to a series of localized adjustments in the tertiary structure, brought about by changes in the hydrogen bond interactions or electrostatic interactions between different residues in the globular folded protein. The preexchange life times of these adjustments range from a fraction of a millisecond to a few milliseconds.