β‐Turn propensities as paradigms for the analysis of structural motifs to engineer protein stability
β‐Turn propensities as paradigms for the analysis of structural motifs to engineer protein stability
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β-转角倾向作为结构基序分析范例以工程蛋白质稳定性
作者：
E. Ohage;W. Graml;Monika M. Walter;Boris Steipe;S. Steinbacher
蛋白质的热力学稳定性为蛋白质序列和天然结构的关系提供了实验指标。我们研究了一种基于结构数据库分析的方法，用于免疫球蛋白可变域的稳定性工程。预测β-转角基序特定位置中最常出现的残基会增加通过定点诱变构建的突变体的折叠稳定性。即使在免疫球蛋白序列中不同残基保守的位置，预测也得到了证实。通常，β-转角倾向增加的突变体表现出折叠协同性增加，这表明对未折叠状态的显着影响与对构象熵的预期影响无关。我们的结论是，主要具有局部相互作用的结构基序可以作为模板，通过该模板可以从蛋白质结构数据库中提取序列偏好模式。这种偏好可以预测突变对蛋白质工程和设计的稳定性影响。
The thermodynamic stability of a protein provides an experimental metric for the relationship of protein sequence and native structure. We have investigated an approach based on an analysis of the structural database for stability engineering of an immunoglobulin variable domain. The most frequently occurring residues in specific positions of β‐turn motifs were predicted to increase the folding stability of mutants that were constructed by site‐directed mutagenesis. Even in positions in which different residues are conserved in immunoglobulin sequences, the predictions were confirmed. Frequently, mutants with increased β‐turn propensities display increased folding cooperativities, suggesting pronounced effects on the unfolded state independent of the expected effect on conformational entropy. We conclude that structural motifs with predominantly local interactions can serve as templates with which patterns of sequence preferences can be extracted from the database of protein structures. Such preferences can predict the stability effects of mutations for protein engineering and design.
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影响因子：
5.6
作者：
DYSON, HJ;RANCE, M;WRIGHT, PE
通讯作者：
WRIGHT, PE
影响因子：
5.6
作者：
RENNELL, D;BOUVIER, SE;POTEETE, AR
通讯作者：
POTEETE, AR
DOI：
10.1016/s0021-9258(18)37859-1
发表时间：
1988-08
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
C. Pace;G. Grimsley;J. A. Thomson;B J Barnett
通讯作者：
C. Pace;G. Grimsley;J. A. Thomson;B J Barnett
影响因子：
56.9
作者：
GW Zhou;Jeffrey Z. Guo;Wei Huang;Robert J. Fletterick;TS Scanlan
通讯作者：
GW Zhou;Jeffrey Z. Guo;Wei Huang;Robert J. Fletterick;TS Scanlan
影响因子：
56.9
作者：
BLABER, M;ZHANG, XJ;MATTHEWS, BW
通讯作者：
MATTHEWS, BW