STRUCTURAL STUDIES OF NATURAL AND ENGINEERED ALLOSTERIC PROTEINS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 设想将效应物诱导的构象变化人工工程化为蛋白质和生物材料，以允许通过外部效应物精确控制催化过程。然而，允许蛋白质变构变化的结构机制却知之甚少。我们实验室的研究重点是通过组合和合理设计程序的组合来设计变构蛋白。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选定的靶蛋白。随后工程化特异性稳定相互作用，以通过特异性效应分子的结合在允许的条件下特异性恢复功能。需要详细的结构表征，以提高对变构开关的理解，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.