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.
The CopC Family: Structural and Bioinformatic Insights into a Diverse Group of Periplasmic Copper Binding Proteins. Lawton TJ, Kenney GE, Hurley JD, and Rosenzweig AC. Biochemistry. 2016 April 19;55(15):2278-2290.
Cell-free protein synthesis enables high yielding synthesis of an active multicopper oxidase. Li J, Lawton TJ, Kostecki JS, Nisthal A, Fang J, Mayo SL, Rosenzweig AC, and Jewett MC. Biotechnology Journal. 2016 February;11(2):212-218.
A new metal binding domain involved in cadmium, cobalt and zinc transport. Smith AT, Barupala D, Stemmler TL, and Rosenzweig AC. Nature Chemical Biology. 2015 September;11(9):678-684.
Enzymatic Oxidation of Methane. Sirajuddin S and Rosenzweig AC. Biochemistry. 2015 April 14;54(14):2283-2294.
Structure and Protein–Protein Interactions of Methanol Dehydrogenase from Methylococcus capsulatus (Bath). Culpepper MA and Rosenzweig AC. Biochemistry. 2014 October 7;53(39):6211-6219.
Identification of the Valence and Coordination Environment of the Particulate Methane Monooxygenase Copper Centers by Advanced EPR Characterization. Culpepper MA, Cutsail GE, Gunderson WA, Hoffman BM, and Rosenzweig AC. Journal of the American Chemical Society. 2014 August 20;136(33):11767-11775.
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.
Diversity of the metal-transporting P1B-type ATPases. Smith AT, Smith KP, and Rosenzweig AC. Journal of Biological Inorganic Chemistry. 2014 August;19(6):947-960.
Characterization of a Cross-Linked Protein–Nucleic Acid Substrate Radical in the Reaction Catalyzed by RlmN. Silakov A, Grove TL, Radle MI, Bauerle MR, Green MT, Rosenzweig AC, Boal AK, and Booker SJ. Journal of the American Chemical Society. 2014 June 11;136(23):8221-8228.
Perspective: what is known, and not known, about the connections between alkane oxidation and metal uptake in alkanotrophs in the marine environment. Austin RN, Kenney GE, and Rosenzweig AC. Metallomics. 2014 June 1;6(6):1121-1125.
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.
View all publications by Amy C. Rosenzweig listed in the National Library of Medicine (PubMed). Current and former IBiS students in blue.