Metal Ions in biology allow for an expanded chemical repertoire with the local protein environment and metal coordination sphere acting synergistically to impart unusual capabilities. It is therefore not surprising that the reactions catalyzed by metalloenzymes are chemically challenging and essential for life. This proposal focuses the complex metalloenzymes involved in anaerobic CO2 fixation. With greenhouse gases and climate change receiving renewed attention due to Superstorm 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.
Our structure/function studies of the enzymes of the Wood-Ljungdahl pathway of anaerobic carbon dioxide fixation provide insight into how microbes can convert a greenhouse gas into a metabolic carbon source. Our findings have applications in the synthesis of biomimetic catalysts for environmental remediation, in the engineering of biosynthetic pathways for the conversion of carbon dioxide into biofuels, and in the design of antiparasitic medicines. With climate change emerging as a major health concern, these studies are timely.
|Bridwell-Rabb, Jennifer; Drennan, Catherine L (2017) Vitamin B12 in the spotlight again. Curr Opin Chem Biol 37:63-70|
|Nakashige, Toshiki G; Zygiel, Emily M; Drennan, Catherine L et al. (2017) Nickel Sequestration by the Host-Defense Protein Human Calprotectin. J Am Chem Soc 139:8828-8836|
|Bowman, Sarah E J; Bridwell-Rabb, Jennifer; Drennan, Catherine L (2016) Metalloprotein Crystallography: More than a Structure. Acc Chem Res 49:695-702|
|Gibson, Marcus I; Chen, Percival Yang-Ting; Drennan, Catherine L (2016) A structural phylogeny for understanding 2-oxoacid oxidoreductase function. Curr Opin Struct Biol 41:54-61|
|Meyer, Peter A; Socias, Stephanie; Key, Jason et al. (2016) Data publication with the structural biology data grid supports live analysis. Nat Commun 7:10882|
|Wittenborn, Elizabeth C; Jost, Marco; Wei, Yifeng et al. (2016) Structure of the Catalytic Domain of the Class I Polyhydroxybutyrate Synthase from Cupriavidus necator. J Biol Chem 291:25264-25277|
|Gibson, Marcus I; Chen, Percival Yang-Ting; Johnson, Aileen C et al. (2016) One-carbon chemistry of oxalate oxidoreductase captured by X-ray crystallography. Proc Natl Acad Sci U S A 113:320-5|
|Gagnon, Derek M; Brophy, Megan Brunjes; Bowman, Sarah E J et al. (2015) Manganese binding properties of human calprotectin under conditions of high and low calcium: X-ray crystallographic and advanced electron paramagnetic resonance spectroscopic analysis. J Am Chem Soc 137:3004-16|
|Jost, Marco; Fernández-Zapata, Jésus; Polanco, María Carmen et al. (2015) Structural basis for gene regulation by a B12-dependent photoreceptor. Nature 526:536-41|
|Jost, Marco; Simpson, Jeffrey H; Drennan, Catherine L (2015) The Transcription Factor CarH Safeguards Use of Adenosylcobalamin as a Light Sensor by Altering the Photolysis Products. Biochemistry 54:3231-4|
Showing the most recent 10 out of 37 publications