STRUCTURAL STUDIES OF NATURAL AND ENGINEERED ALLOSTERIC PROTEINS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 将效应器诱导的构象变化转化为蛋白质和生物材料的人工工程被设想为允许通过外部效应器精确控制催化过程。然而，蛋白质中允许变构变化的结构机制还知之甚少。我们实验室的研究重点是通过组合和合理的设计程序来设计变构蛋白。使用我们实验室开发的新方法，我们将不稳定的点突变引入到选定的目标蛋白中。具体地说，稳定的相互作用随后被设计来恢复功能，特别是在允许的条件下，通过结合特定的效应分子。需要详细的结构表征，以促进对变构开关的总体理解，并优化和改进所开发的方法。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The artificial engineering of effector-induced conformational changes into proteins and biomaterials is envisioned to allow for the precise control of catalytic processes via external effectors. The structural mechanisms that permit allosteric changes in proteins, however, are only poorly understood. Research in our laboratory focuses on the design of allosteric proteins through a combination of combinatorial- and rational design procedures. Using new methodology developed in our laboratory we introduce destabilizing point mutations into selected target proteins. Specifically stabilizing interactions are engineered subsequently to restore function specifically under permissible conditions through the binding of specific effector molecules. Detailed structural characterizations are required to advance understanding of allosteric switches in general, and to optimize and improve the developed methodology.