Shelagh 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

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.

Mills DA, Xu S, Geren L, Hiser C, Qin L, Sharpe MA, McCracken J, Durham B, Millett F, Ferguson-Miller S. Proton-dependent electron transfer from CuA to heme a and altered EPR spectra in mutants close to heme a of cytochrome oxidase. Biochemistry. 2008 Nov 4;47(44):11499-509.

Sharpe MA, Ferguson-Miller S. A chemically explicit model for the mechanism of proton pumping in heme-copper oxidases. J Bioenerg Biomembr. 2008 Oct;40(5):541-9.

Qin L, Mills DA, Buhrow L, Hiser C, Ferguson-Miller S. A conserved steroid binding site in cytochrome C oxidase. Biochemistry. 2008 Sep 23;47(38):9931-3.

Qin L, Sharpe MA, Garavito RM, Ferguson-Miller S. Conserved lipid-binding sites in membrane proteins: a focus on cytochrome c oxidase. Curr Opin Struct Biol. 2007 Aug;17(4):444-50. Review.

Qin L, Mills DA, Hiser C, Murphree A, Garavito RM, Ferguson-Miller S, Hosler J. Crystallographic location and mutational analysis of Zn and Cd inhibitory sites and role of lipidic carboxylates in rescuing proton path mutants in cytochrome c oxidase. Biochemistry. 2007 May 29;46(21):6239-48.

Xu J, Sharpe MA, Qin L, Ferguson-Miller S, Voth GA. Storage of an excess proton in the hydrogen-bonded network of the d-pathway of cytochrome C oxidase: identification of a protonated water cluster. J Am Chem Soc. 2007 129(10):2910-3. MORE