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 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 investigating the mechanisms of these enzymes, it is also essential to understand the regulation of the levels of the trace minerals required for metallocenter assembly. Here we propose to study the structure and mechanism of enzymes involved in carbon monoxide oxidation and acetyl-CoA synthesis: the Ni requiring carbon monoxide dehydrogenase/acetyl-CoA synthases (CODH/ACS), corrinoid Fe-S protein (CFeSP), methyltetrahydrofolate-CFeSP methyltransferase (MeTr). To explore cellular Ni uptake, we will investigate the structure and mechanism of Ni-regulatory protein NikR. ? ?
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 |
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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 |
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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