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.
Effects of Zinc on Particulate Methane Monooxygenase Activity and Structure. Sirajuddin S, Barupala D, Helling S, Marcus K, Stemmler TL, and Rosenzweig AC. Journal of Biological Chemistry. 2014 August 1;289(31):21782-21794.
Mechanism of the C5 Stereoinversion Reaction in the Biosynthesis of Carbapenem Antibiotics. Chang W, Guo Y, Wang C, Butch SE, Rosenzweig AC, Boal AK, Krebs C, and Bollinger JM. Science. 2014 March 7;343(6175):1140-1144.
Streptococcus sanguinis Class Ib Ribonucleotide Reductase: high activity with both iron and manganese cofactors and structural insights. Makhlynets O, Boal AK, Rhodes DV, Kitten T, Rosenzweig AC, and Stubbe J. Journal of Biological Chemistry. 2014 February 28;289(9):6259-6272.
Sinorhizobium meliloti Nia is a P1B-5-ATPase expressed in the nodule during plant symbiosis and is involved in Ni and Fe transport. Zielazinski EL, González-Guerrero M, Subramanian P, Stemmler TL, Argüello JM, and Rosenzweig AC. Metallomics. 2013 December 1;5(12):1614-1623.
Structural Basis for Assembly of the MnIV/FeIII Cofactor in the Class Ic Ribonucleotide Reductase from Chlamydia trachomatis. Dassama LMK, Krebs C, Bollinger JM, Rosenzweig AC, and Boal AK. Biochemistry. 2013 September 17;52(37):6424-6436.
Characterization of a Nitrite Reductase Involved in Nitrifier Denitrification. Lawton TJ, Bowen KE, Sayavedra-Soto LA, Arp DJ, and Rosenzweig AC. Journal of Biological Chemistry. 2013 August 30;288(35):25575-25583.
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.
View all publications by Amy C. Rosenzweig listed in the National Library of Medicine (PubMed). Current and former IBiS students in blue.