Amy C. Rosenzweig
Weinberg Family Distinguished Professor of Life Sciences
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.
Genome mining for methanobactins. Kenney GE and Rosenzweig AC. BMC Biology. 2013 February 26;11:17.
Characterization of a Cobalt-Specific P1B-ATPase. Zielazinski EL, Cutsail GE, Hoffman BM, Stemmler TL, and Rosenzweig AC. Biochemistry. 2012 October 9;51(40):7891-7900.
Evidence for Oxygen Binding at the Active Site of Particulate Methane Monooxygenase. Culpepper MA, Cutsail GE, Hoffman BM, and Rosenzweig AC. Journal of the American Chemical Society. 2012 May 9;134(18):7640-7643.
The Dimanganese(II) Site of Bacillus subtilis Class Ib Ribonucleotide Reductase. Boal AK, Cotruvo JA, Stubbe J, and Rosenzweig AC. Biochemistry. 2012 May 8;51(18):3861-3871.
Chemistry and Biology of the Copper Chelator Methanobactin. Kenney GE and Rosenzweig AC. ACS Chemical Biology. 2012 February 17;7(2):260-268.
Evidence That the β Subunit of Chlamydia trachomatis Ribonucleotide Reductase Is Active with the Manganese Ion of Its Manganese(IV)/Iron(III) Cofactor in Site 1. Dassama LMK, Boal AK, Krebs C, Rosenzweig AC, and Bollinger JM. Journal of the American Chemical Society. 2012 February 8;134(5):2520-2523.
Toward a Molecular Understanding of Metal Transport by P1B-Type ATPases. Rosenzweig AC and Argüello JM. Current Topics in Membranes. 2012;69:113-136.
Crystal Structure and Characterization of Particulate Methane Monooxygenase from Methylocystis species Strain M. Smith SM, Rawat S, Telser J, Hoffman BM, Stemmler TL, and Rosenzweig AC. Biochemistry. 2011 November 29;50(47):10231-10240.
Dual Pathways for Copper Uptake by Methanotrophic Bacteria. Balasubramanian R, Kenney GE, and Rosenzweig AC. Journal of Biological Chemistry. 2011 October 28;286(43):37313-37319.
Structural Basis for Methyl Transfer by a Radical SAM Enzyme. Boal AK, Grove TL, McLaughlin MI, Yennawar NH, Booker SJ, and Rosenzweig AC. Science. 2011 May 27;332(6033):1089-1092.
Detection and Characterization of a Multicopper Oxidase from Nitrosomonas europaea. Lawton TJ and Rosenzweig AC. Methods in Enzymology. 2011;496:423-433.
View all publications by Amy C. Rosenzweig listed in the National Library of Medicine (PubMed). Current and former IBiS students in blue.