Faculty
Amy C. Rosenzweig, PhD
Associate Professor
Molecular Biosciences/Chemistry
PhD, MIT
Email: amyr@northwestern.edu
Phone: (847) 467-5301
Fax: (847) 467-6489
Room: Cook Rm 4137
Research Interests
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.
Selected Publications
Structural biology of copper trafficking. Boal AK, Rosenzweig AC. Chem Rev. 2009 Oct;109(10):4760-79. No abstract available.
Crystal structures of cisplatin bound to a human copper chaperone. Boal AK, Rosenzweig AC. J Am Chem Soc. 2009 Oct 14;131(40):14196-7.
Structure of the redox sensor domain of Methylococcus capsulatus (Bath) MmoS. Ukaegbu UE, Rosenzweig AC. Biochemistry. 2009 Mar 17;48(10):2207-15.
Crystal structure of a two-domain multicopper oxidase: implications for the evolution of multicopper blue proteins. Lawton TJ, Sayavedra-Soto LA, Arp DJ, Rosenzweig AC. J Biol Chem. 2009 Apr 10;284(15):10174-80. Epub 2009 Feb 17.
The metal centres of particulate methane mono-oxygenase. Rosenzweig AC. Biochem Soc Trans. 2008 Dec;36(Pt 6):1134-7. Review.
Copper methanobactin: a molecule whose time has come. Balasubramanian R, Rosenzweig AC. Curr Opin Chem Biol. 2008 Apr;12(2):245-9. Epub 2008 Mar 17. Review.
Characterization and structure of a Zn2+ and [2Fe-2S]-containing copper chaperone from Archaeoglobus fulgidus. Sazinsky MH, LeMoine B, Orofino M, Davydov R, Bencze KZ, Stemmler TL, Hoffman BM, Argüello JM, Rosenzweig AC. J Biol Chem. 2007 Aug 31;282(35):25950-9. Epub 2007 Jul 3.
Biochemical characterization of MmoS, a sensor protein involved in copper-dependent regulation of soluble methane monooxygenase. Ukaegbu UE, Henery S, Rosenzweig AC. Biochemistry. 2006 Aug 29;45(34):10191-8.
View all publications by Amy C. Rosenzweig listed in the National Library of Medicine (PubMed). Past and current IBiS students in blue