Assessment of conformational parameters as predictors of limited proteolytic sites in native protein structures
Assessment of conformational parameters as predictors of limited proteolytic sites in native protein structures
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DOI：
10.1093/protein/11.5.349
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发表时间：
1998-05-01
期刊：
影响因子：
--
通讯作者：
Thornton, JM
中科院分区：
文献类型：
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作者：
Hubbard, SJ;Beynon, RJ;Thornton, JM
尽管有限的蛋白质分解在生物系统中很重要，但仅仅给出一个简单的序列特异性，通常很难合理地解释为什么一个蛋白酶能水解一个特定的键。了解限制蛋白质降解的结构性质是控制和操纵这一现象的第一步。在已知三级结构的蛋白质中，已产生一组扩展的缺口位点，被狭窄和广泛的特异性蛋白酶切割，产生了严格有限的位点的稳健数据集。对一组扩展的构象参数的关键评估显示，与有限的蛋白水解点有很强的相关性，尽管它们只是孤立的适度预测因素。当构象参数组合在允许通过Metropolis搜索协议比较它们的相对重要性的加权预测方案中时，总体预测能力显著提高。这些参数的一个子集同样表现良好，显示了敏感性的关键决定因素。派生的预测算法已通过互联网提供。文中还讨论了它对预测其他表面相关特征的作用。
Despite the importance of limited proteolysis in biological systems it is often difficult to rationalize why a proteinase hydrolyses a particular bond, given a simple sequence specificity alone. Understanding of the structural properties limiting the proteolysis represents a first step on the pathway to control and manipulation of this phenomena. An expanded set of nick-sites in proteins of known tertiary structure, cut by both narrow and broad specificity proteinases, has been generated yielding a robust data set of strictly limited sites. A critical evaluation of an expanded set of conformational parameters revealed a strong correlation with limited proteolytic sites, although they are only modest predictors in isolation. The overall predictive power is significantly improved when the conformational parameters are combined in a weighted predictive scheme that permits their relative importance to be compared via a Metropolis search protocol. A subset of the parameters performs equally well demonstrating the key determinants of susceptibility. The derived predictive algorithm has been made available via the internet. Its utility for predicting other surface-correlated features is also discussed.