STRUCTURAL STUDIES OF NATURAL AND ENGINEERED ALLOSTERIC PROTEINS

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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.