Complex Metallocluster Structure and Assembly

Massachusetts Institute Of Technology, Cambridge MA

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Abstract

DESCRIPTION (provided by applicant): Metal ions in biology allow for an expanded chemical repertoire with the local protein environment and metal coordination sphere acting synergistically imparting unusual capabilities. It is therefore not surprising that the reactions catalyzed by metalloenzymes are chemically challenging and essential for life. This proposal focuses on the complex metalloenzymes involved in anaerobic CO2 fixation. With greenhouse gases and climate change receiving renewed attention due to Super Storm Sandy and the recent droughts in the Midwest, we seek to understand the chemistry by which microbes convert the greenhouse gas CO2 into a metabolic carbon source. Our approach involves a variety of biophysical methods, which will allow us to visualize the hand-off of one-carbon units between enzymes in this pathway, as well as to probe the structural basis for enzymatic generation of low-potential electrons, which drive the chemistry of the pathway. By combining X-ray crystallography, small-angle X-ray scattering, analytical ultracentrifugation, isothermal titration calorimetry, and electron microscopy, we will explore the mechanism of action of the complex metalloenzymes in anaerobic CO2 fixation.