Toward an understanding of the sequence and structural basis of allosteric proteins
Toward an understanding of the sequence and structural basis of allosteric proteins
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了解变构蛋白的序列和结构基础
DOI：
10.1016/j.jmgm.2012.12.011
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发表时间：
2013-03-01
影响因子：
2.9
通讯作者：
Zhang, Jian
中科院分区：
文献类型：
--
作者：
Li, Xiaobai;Chen, Yingyi;Zhang, Jian
变构是调节蛋白质功能的最有效的手段，从代谢机制的控制到信号转导途径。尽管变构调节已经被认识了半个世纪，但我们对变构蛋白的特性以及变构位点和调节剂的结构耦合的了解还很有限。本文对变构蛋白进行了全面的分析，揭示了变构蛋白中的一系列共同特征，从而揭示了变构相互作用的基础。变构蛋白主要出现在转移酶中，而磷酸化是变构蛋白中最常见的修饰类型。与变构蛋白相关的疾病主要包括代谢性疾病和癌症。通常，变构蛋白倾向于以单体或偶数多聚体的形式存在。变构蛋白比普通蛋白具有更大的稳定性和疏水性。对变构中心的进一步分析揭示了一系列埋藏的致密口袋，其疏水表面积比相应的正构中心大得多。在对106个不同的变构蛋白-调节剂对的分析中观察到，变构中心的疏水性在变构调节剂的结合中起主导作用。这些结果可能对预测哪些蛋白质是变构的，以及设计新的触发器来抑制或激活感兴趣的蛋白质具有重要意义。(C)2013 Elsevier Inc.保留所有权利。
Allostery is the most efficient means of regulating protein functions, ranging from the control of metabolic mechanisms to signal transduction pathways. Although allosteric regulation has been recognized for half a century, our knowledge is limited to the characteristics of allosteric proteins and the structural coupling of allosteric sites and modulators. In this paper, we present a comprehensive analysis of allosteric proteins that provides insight into the foundation of allosteric interactions by revealing a series of common features in the allosteric proteins. Allosteric proteins mainly appear in transferases, and phosphorylation is the most common type of modification found in allosteric proteins. Disorders related to allosteric proteins primarily comprise metabolic diseases and cancers. In general, allosteric proteins prefer to exist as monomers or even-numbered multimers. Greater stability and hydrophobicity are observed in allosteric proteins than in general proteins. Further analysis of the allosteric sites reveals a series of buried and compact pockets composed of significantly greater hydrophobic surface area than the corresponding orthosteric sites. The hydrophobicity of the allosteric sites plays a dominant role in the binding of allosteric modulators as observed in the analysis of 106 diverse allosteric protein-modulator pairs. These results may be of great significance in predicting which proteins are allosteric and in designing novel triggers to inhibit or activate proteins of interest. (C) 2013 Elsevier Inc. All rights reserved.