Metal ions in biology allow for an expanded chemical repertoire;the local protein environment and metal coordination sphere act synergistically to confer unique reactivity. It is therefore not surprising that the reactions catalyzed by metalloenzymes are chemically challenging and essential for life. We use X-ray crystallography and computation to study the structure and mechanism of complex metallocofactors. Our findings have applications for the synthesis of biomimetic catalysts and in the design of enzyme inhibitors. In addition to interrogating the mechanisms of metalloenzymes, it is important to investigate the cellular regulation of trace mineral levels required for metallocenter assembly, as well as to study the assembly process itself. This proposal focuses on nickel and iron-sulfur containing proteins and their metallochaperones, as well as the regulation of nickel uptake and iron-sulfur cluster assembly.
The proposed research uses X-ray crystallography and computation as the chief tools to investigate nickel, iron-sulfur and corrinoid containing proteins, with a focus on proteins involved in one-carbon metabolism. Our goals are to explore the mechanism and assembly of complex metallocofactors, as well as the cellular regulation of nickel uptake and iron-sulfur cluster biogenesis.
| 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 |
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