Analysis of void volumes in proteins and application to stability of the p53 tumour suppressor protein
Analysis of void volumes in proteins and application to stability of the p53 tumour suppressor protein
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DOI：
10.1016/j.jmb.2004.10.015
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发表时间：
2004-12-10
影响因子：
5.6
通讯作者：
Martin, ACR
中科院分区：
文献类型：
--
作者：
Cuff, AL;Martin, ACR
我们开发了一种新方法来分析蛋白质中的空隙（定义为溶剂无法进入的空腔）。该方法将单个离散空隙的分析与填充质量的分析结合起来。虽然这些是同一效应的不同方面，但传统上使用不同的方法对它们进行分析。该方法已应用于计算一组非冗余蛋白质结构域中的总空隙体积和最大空隙尺寸，并已用于检查热稳定性和空隙尺寸之间的相关性。然后将肿瘤抑制蛋白 p53 与非冗余数据集进行比较，以确定其低热稳定性是否是由于包装不良造成的。我们发现 p53 具有平均堆积，但在癌症中观察到的一些先前无法解释的 p53 突变的有害影响可以通过异常大的空隙的产生来解释。 (C) 2004 Elsevier Ltd. 保留所有权利。
We have developed a new method for the analysis of voids in proteins (defined as empty cavities not accessible to solvent). This method combines analysis of individual discrete voids with analysis of packing quality. While these are different aspects of the same effect, they have traditionally been analysed using different approaches. The method has been applied to the calculation of total void volume and maximum void size in a non-redundant set of protein domains and has been used to examine correlations between thermal stability and void size. The tumour-suppressor protein p53 has then been compared with the non-redundant data set to determine whether its low thermal stability results from poor packing. We found that p53 has average packing, but the detrimental effects of some previously unexplained mutations to p53 observed in cancer can be explained by the creation of unusually large voids. (C) 2004 Elsevier Ltd. All rights reserved.