Shelagh M. Ferguson-Miller
Research Interests
Electron transfer
coupled to proton translocation is the basic mechanism of energy
generation in most living organisms, but the molecular mechanism is not
understood. A key enzyme in all eukaryotic and most prokaryotic electron
transfer systems is cytochrome c oxidase, 
which accepts electrons
derived from food and donates them to oxygen, generating a pH and
electrical gradient to drive ATP synthesis.
We are studying mammalian,
plant and bacterial cytochrome c oxidases which differ in peptide
composition but carry out the same reactions using the same metal centers
to catalyze the process. Each of these enzymes offers different advantages
for investigating the molecular mechanism of energy transduction by a
variety of approaches, including kinetic analysis, chemical modification,
physical/spectral techniques, genetic engineering and crystallography. To
understand the molecular basis of electron transfer and coupled proton
translocation, mutants have been prepared in highly conserved residues
predicted to be metal ligands or proton ligands. MORE
Recent Publications
Nowak C, Laredo T, Gebert J, Lipkowski J, Gennis RB, Ferguson-Miller S, Knolla W, Naumann RLC. (2011) 2D-SEIRA spectroscopy to highlight conformational changes of the cytochrome c oxidase induced by direct electron transfer. Metallomics 3:619-627.
X Zhang, B Tamot, C Hiser, GE Reid, C Benning, S Ferguson-Miller. 2011. Cardiolipin deficiency in Rhodobacter sphaeroides alters the lipid profile of membranes and of crystallized cytochrome oxidase, but structure and function are maintained. Biochemistry 50:3879-3890.
X Zhang, C Hiser, B Tamot, C Benning, GE Reid, S Ferguson-Miller. 2011. Combined genetic and metabolic manipulation of lipids in Rhodobacter sphaeroides reveals non-phospholipid substitutions in fully active cytochrome c oxidase. Biochemistry 50:3891-3902.
Liu JA, Qin L, Ferguson-Miller S. Crystallographic and online spectral evidence for role of conformational change and conserved water in cytochrome oxidase proton pump. P. Natl. Acad. Sci. USA 2011 (108) 1284-1289.
Nowak C, Schach D, Gebert J, Grosserueschkamp M, Gennis RB, Ferguson-Miller S, Knoll W, Walz D, Naumann RLC. Oriented immobilization and electron transfer to the cytochrome c oxidase. Journal of Solid State Electrochemistry 2011 (15) 105-114.
Schach D, Nowak C, Gennis RB, Ferguson-Miller S, Knoll W, Walz D, Naumann RLC: Modeling direct electron transfer to a multi-redox center protein Cytochrome c oxidase. Journal of Electroanalytical Chemistry 2010 Nov 15;649:268-276.
Nowak C, Santonicola MG, Schach D, Zhu JP, Gennis RB, Ferguson-Miller S, Baurecht D, Walz D, Knoll W, Naumann RLC. Conformational transitions and molecular hysteresis of cytochrome c oxidase: Varying the redox state by electronic wiring. Soft Matter. 2010 (6) 5523-5532.
Qin L, Liu J, Mills DA, Proshlyakov DA, Hiser C, Ferguson-Miller S. Redox-dependent conformational changes in cytochrome C oxidase suggest a gating mechanism for proton uptake. Biochemistry. 2009 Jun 16;48(23):5121-30.
Zhang X, Ferguson-Miller SM, Reid GE. Characterization of ornithine and glutamine lipids extracted from cell membranes of Rhodobacter sphaeroides. J Am Soc Mass Spectrom. 2009 Feb;20(2):198-212.
Sharpe MA, Krzyaniak MD, Xu S, McCracken J, Ferguson-Miller S. EPR evidence of cyanide binding to the Mn(Mg) center of cytochrome c oxidase: support for Cu(A)-Mg involvement in proton pumping. Biochemistry. 2009 Jan 20;48(2):328-35.
