Structural biology and bioinorganic chemistry, metal uptake, transport and storage, oxygen activation by metalloenzymes, biological methane oxidation, membrane protein crystallography

The goal of our research program is to understand metalloprotein function on the molecular level by using X-ray crystallographic, biophysical, and biochemical techniques.   Projects in the laboratory are divided into two areas, metalloenzymes and metal trafficking proteins, with an increasing focus on structural characterization of integral membrane proteins.

We recently determined the molecular structure of Nature's predominant methane oxidation catalyst, a metalloenzyme called particulate methane monooxygenase (pMMO).   pMMO converts methane, the most inert hydrocarbon, to methanol.   This reaction is the first step in the metabolic pathway of methanotrophs, bacteria that use methane as their sole source of carbon and energy.   Knowledge of the pMMO structure and particularly of its catalytic site may impact the use of methane as an alternative energy source by facilitating the development of new synthetic catalysts.   In addition, an understanding of pMMO is relevant to the use of methanotrophs in bioremediation and in strategies to combat global warming since methane is a potent greenhouse gas.   The structure reveals that pMMO adopts a trimeric structure and contains multiple metal ions, including three coppers and a zinc.   Current efforts are directed at determining which of the metal centers are involved in methane and dioxygen binding.

We are also studying copper chaperones, soluble proteins that deliver metal ions to specific target proteins by direct protein-protein interactions.   Using both X-ray crystallography and NMR, we have determined structures of copper chaperones involved in copper delivery to Cu + -ATPases, to copper,zinc superoxide dismutase, and to cytochrome c oxidase.   Mutations in Cu + -ATPases, which are integral membrane proteins that couple the energy of ATP hydrolysis to Cu + translocation across membranes, are linked to human disorders of copper metabolism such as Wilson disease and Menkes syndrome.   We are interested in understanding Cu + -ATPase function, including interactions with the copper chaperones and other partner proteins, at the molecular level.

Sazinsky, M. H., Mandal, A. L, Argüello, J. M., & Rosenzweig, A. C. Structure of the ATP binding domain from the Archaeglobus fulgidus Cu 1+ -ATPase. J. Biol. Chem. 281, 11161-11166, 2006.

Hakemian, A. S., Tinberg, C. E., Kondapalli, K. C., Telser, J., Hoffman, B. M., Stemmler, T. L., & Rosenzweig, A. C. The copper chelator methanobactin from Methylosinus trichosporium OB3b binds Cu(I). J. Am. Chem. Soc., 127, 17142-17143, 2005.

Lieberman, R. L & Rosenzweig, A. C. The quest for the particulate methane monooxygenase active site. Dalton Trans. 21, 3390-3396, 2005.

Lieberman, R. L & Rosenzweig, A. C. Crystal structure of a membrane-bound metalloenzyme that catalyses the biological oxidation of methane. Nature 434, 177-182, 2005.

Sommerhalter, M., Lieberman, R. L., & Rosenzweig, A. C. X-ray crystallography and biological metal centers: is seeing believing? Inorg. Chem. 44, 770-778, 2005.

Abajian, C., Yatsunyk, L. A., Ramirez, B. E., & Rosenzweig, A. C. Solution structure and binding of copper(I) by yeast Cox17. J. Biol. Chem. 279, 53584-53592, 2004.

Wernimont, A. K., Yatsunyk, L. A., & Rosenzweig, A. C. Binding of copper(I) by the Wilson disease protein and its copper chaperone. J. Biol. Chem. 269, 12269-12276, 2004.

Lieberman, R. L. & Rosenzweig, A. C. Biological methane oxidation: regulation, biochemistry, and active site structure of particulate methane monooxygenase. Crit. Rev. Biochem. Mol. Biol. 39, 147-164, 2004.

Sommerhalter, M., Voegtli, W. C., Perlstein, D. L., Ge, J., Stubbe, J., & Rosenzweig, A. C. Structures of the yeast ribonucleotide reductase Rnr2 and Rnr4 homodimers. Biochem. 43, 7736-7742, 2004.

View all publications by publications by Amy C. Rosenzweig listed in the National Library of Medicine (PubMed).