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.
| Wittenborn, Elizabeth C; Merrouch, Mériem; Ueda, Chie et al. (2018) Redox-dependent rearrangements of the NiFeS cluster of carbon monoxide dehydrogenase. Elife 7: |
| Nakashige, Toshiki G; Bowman, Sarah E J; Zygiel, Emily M et al. (2018) Biophysical Examination of the Calcium-Modulated Nickel-Binding Properties of Human Calprotectin Reveals Conformational Change in the EF-Hand Domains and His3Asp Site. Biochemistry 57:4155-4164 |
| Chen, Percival Yang-Ting; Aman, Heather; Can, Mehmet et al. (2018) Binding site for coenzyme A revealed in the structure of pyruvate:ferredoxin oxidoreductase from Moorella thermoacetica. Proc Natl Acad Sci U S A 115:3846-3851 |
| Backman, Lindsey R F; Funk, Michael A; Dawson, Christopher D et al. (2017) New tricks for the glycyl radical enzyme family. Crit Rev Biochem Mol Biol 52:674-695 |
| 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 |
| Bridwell-Rabb, Jennifer; Drennan, Catherine L (2017) Vitamin B12in the spotlight again. Curr Opin Chem Biol 37:63-70 |
| Padmanabhan, S; Jost, Marco; Drennan, Catherine L et al. (2017) A New Facet of Vitamin B12: Gene Regulation by Cobalamin-Based Photoreceptors. Annu Rev Biochem 86:485-514 |
| 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 |
| 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 |
Showing the most recent 10 out of 42 publications
