Brian Gibney of Columbia University is supported by the Inorganic, Bioinorganic, and Organometallic Chemistry program for research on de novo design and synthesis of metallo-proteins. Metal-ion binding will be used to initiate a 'flip' of protein configuration between alternative configurations. Detailed study of the characteristics of such synthetic systems will be used to increase understanding of factors that control allostery and cooperativity in enzymes, hemoglobins, and other important biologically occurring systems.
An already-characterized four-helix bundle scaffold will be used to develop a protein that binds two metal centers (a heme and a Zn(II) center) in a cooperative fashion. Completion of this phase of the work will confirm that allostery can be used to design and synthesize functional proteins. Chromatographic and spectroscopic techniques will be used for separations and characterization of products. Fluorescence resonance energy transfer (FRET) experiments, as well as X-ray crystallography, will be used to determine such structural information as distances between protein loop regions. Kinetic studies and ligand-binding investigations will be carried out to support the main research effort. Understanding gained in this project has potential utility in design and fabrication of ultra-small mechanical switches that would be highly useful in biological and/or information-processing applications.
