title: Toward an understanding of the sequence and structural basis of allosteric proteins.
abstract: 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.
authors: Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai JiaoTong University, School of Medicine, Shanghai 200025, China.
authors: Xiaobai
authors: X
authors: Li
authors: Yingyi
authors: Y
authors: Chen
authors: Shaoyong
authors: S
authors: Lu
authors: Zhimin
authors: Z
authors: Huang
authors: Xinyi
authors: X
authors: Liu
authors: Qi
authors: Q
authors: Wang
authors: Ting
authors: T
authors: Shi
authors: Jian
authors: J
authors: Zhang
mesh_terms: D000494:Allosteric Regulation; D000495:Allosteric Site; D000596:Amino Acids; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry* / Q000145:classification
chemical_list: D000596:Amino Acids; D011506:Proteins