Chacón Lab

Research

About the Chacón lab

People may not realize this, but our bodies require a treasure box of metal ions (Fe, Zn, Co, Ni, Cu, Se, Mn) to do otherwise impossible bioinorganic chemistry in the cell! I am fascinated with how life evolved around the use of these metal ions. My undergraduates and I use state-of-the-art spectroscopic techniques (x-ray absorption spectroscopy, native tryptophan fluorescence, and stopped flow/rapid freeze quench intermediate trapping) to study Cu, Fe, Zn, Te and Se binding proteins and enzymes.

The main questions guiding our research are:

1. How are metal ions physically transferred from one metalloprotein to another, and how do these proteins “recognize” one another?
2. How can we best characterize newly discovered metalloproteins?
3. How do organisms biophysically detoxify and extrude otherwise lethal levels of essential (e.g. Cu) and/or non-essential metal ions (e.g. Ag and Te)?
4. Can we better study membrane-bound metalloproteins implicated in metal ion efflux?
5. Can we apply what we know about these systems toward developing tools against antibiotic resistance in pathogenic bacteria, or toward bioremediation of industrially precious (or biologically toxic!) metal ions from the environment?

Publications

Chacón, KN, Mathe ZS, Perkins J, Alwan K, Ho EN, Ucisik MN, Merz K, Blackburn NJ (2018).Trapping Intermediates in Metal Transfer Reactions of the CusCBAF Export Pump of E. coli. Communications Biology (Nature), in press.

Underline denotes Reed College undergraduates.

Yu Y, Petrik I, Chacón KN, Hosseinzadeh P, Chen H, Blackburn NJ, Lu Y (2017). Effect of circular permutation on the structure and function of Type 1 blue copper center in Azurin. Protein Science, 26:218-226

Martin-Diaconescu V*, Chacón KN*,Delgado-Jaime M, Sokaras D, Weng T-C, DeBeer S, Blackburn NJ (2017).  Kβ Valence-to-core x-ray emission studies of Cu(I) binding proteins with mixed methionine-histidine coordination. Relevance to the reactivity of the M- and H-sites of peptidylglycine monooxygenase. Inorganic Chemistry 55:3431-9    

*Shared primary authorship.

Farashishiko A, Chacón KN, Blackburn NJ, Woods M (2016). Nano assembly and encapsulation; a versatile platform for slowing the rotation of polyanionic Gd3+-based MRI contrast agents. Contrast Media and Molecular Imaging. 11:154-9

Hosseinzadeh P, Marshall NM, Chacón KN,Yu Y, Nilges MJ, New SY, Tashkov SA, Blackburn NJ, Lu Y (2016). Design of a single protein that spans the entire 2V range of physiological redox potentials. Proceedings of the National Academy of Sciences USA.113:262-7

Chakraborty S, Polen MJ, Chacón KN, Wilson TD, Yu Y, Reed J, Nilges MJ, Blackburn NJ, Lu Y (2015). Binuclear CuA formation in biosynthetic models of CuA in azurin proceeds via a novel Cu(Cys)2His mononuclear copper intermediate. Biochemistry. 54: 6071–6081.

Butterfield CN, Tao L, Chacón KN,Spiro TG, Blackburn NJ, Casey WH, Britt RD, Tebo BM (2015). Multicopper manganese oxidase accessory proteins bind Cu and heme. Biochim Biophys Acta.1854: 1853–1859.

Chacón KN, Mealman TD, McEvoy M, Blackburn NJ (2014). A metal mediated sensor-switch controls the Ag/Cu efflux pump in E. coli. Proceedings of the National Academy of Sciences USA.111: 15373–15378.

Chacón KN, Blackburn NJ (2012). Stable Cu(II) and Cu(I) mononuclear intermediates in the assembly of the CuA center of Thermus thermophilus cytochrome oxidase. Journal of the American Chemical Society 134: 16401–16412.

Mealman, TD, Zhou M, Affandi T, Chacón KN, Aranguren ME, Blackburn NJ, Wysocki VH, McEvoy MM (2012). N-terminal region of CusB is sufficient for metal binding and metal transfer with the metallochaperone CusF. Biochemistry 51: 6767–6775.