Journal
JOURNAL OF MOLECULAR GRAPHICS & MODELLING
Volume 40, Issue -, Pages 30-39Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jmgm.2012.12.011
Keywords
Allostery; Allosteric protein; Allosteric site; Orthosteric site
Categories
Funding
- National Basic Research Program of China (973 Program) [2012CB967001]
- National Natural Science Foundation of China [21002062, 21102090]
- Foundation for the Author of National Excellent Doctoral Dissertation of PR China [201083]
- Shanghai Jiao Tong University K. C. Wong Medical Fellowship Fund
- Innovative Research Team of Shanghai Municipal Education Commission
- Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning
- Shanghai PuJiang Program [10PJ406800]
- China Postdoctoral Science Foundation [2012M520046]
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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.
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