Bowler Bruce E
Department of Chemistry, University of Montana, Missoula, MT 59812, USA.
Mol Biosyst. 2007 Feb;3(2):88-99. doi: 10.1039/b611895j. Epub 2006 Nov 7.
Recent work on the thermodynamics of protein denatured states is providing insight into the stability of residual structure and the conformational constraints that affect the disordered states of proteins. Current data from native state hydrogen exchange and the pH dependence of protein stability indicate that residual structure can modulate the stability of the denatured state by up to 4 kcal mol(-1). NMR structural data have emphasized the role of hydrophobic clusters in stabilizing denatured state residual structures, however recent results indicate that electrostatic interactions, both favorable and unfavorable, are also important modulators of the stability of the denatured state. Thermodynamics methods that take advantage of histidine-heme ligation chemistry have also been developed to probe the conformational constraints that act on denatured states. These methods have provided insights into the role of excluded volume, chain stiffness, and loop persistence in modulating the conformational preferences of highly disordered proteins. New insights into protein folding and novel methods to manipulate protein stability are emerging from this work.
近期关于蛋白质变性状态热力学的研究，正在为深入了解残余结构的稳定性以及影响蛋白质无序状态的构象限制提供线索。来自天然态氢交换和蛋白质稳定性的pH依赖性的当前数据表明，残余结构可将变性状态的稳定性调节高达4千卡/摩尔（-1）。核磁共振结构数据强调了疏水簇在稳定变性状态残余结构中的作用，然而最近的结果表明，有利和不利的静电相互作用也是变性状态稳定性的重要调节剂。利用组氨酸-血红素连接化学的热力学方法也已被开发出来，以探究作用于变性状态的构象限制。这些方法为排除体积、链刚性和环持续性在调节高度无序蛋白质的构象偏好中的作用提供了见解。这项工作正在产生关于蛋白质折叠的新见解和操纵蛋白质稳定性的新方法。
