faculty

Professor of Chemistry
Ph.D., Stanford University

Biophysical Chemistry and Inorganic Spectroscopy. Bioinorganic Chemistry of Mn and Zn. Organometallic Chemistry of Cu.

Phone: (734) 764-7324
E-mail: jeph@umich.edu

Research Group

Metalloenzymes (proteins with metals at their active sites) catalyze reactions with a speed and selectivity that is unrivaled by conventional catalysts. We want to understand how metalloenzymes work. Our approach is to correlate metal-site structure with enzymatic function. Currently, we are studying manganese redox enzymes and zinc containing proteins.

Virtually all of the O₂ in the atmosphere is produced by the photosynthetic oxygen evolving complex, a Mn/Ca/Cl cluster that catalyzes the oxidation of H₂O to O₂. Other manganese enzymes include Mn catalase and superoxide dismutase. By comparing these Mn structures, we have been able to develop a better understanding of the bioinorganic chemistry of Mn. Our ultimate goal is to understand, in detail, how plants make oxygen.

Zn has recently been shown to play a critical role in catalyzing the transfer of alkyl groups to thiol acceptors, forming thioethers. The enzymes, which are involved in a number of critical reactions, ranging from homocysteine homeostasis to protein farnesylation to alkene metabolism, generally contain thiolate-rich Zn sites. We want to understand the mechanism of Zn-promoted alkyl transfer. How does Zn(II) promote nucleophilic attack of a thiol on an alkyl donor?

In addition to its enzymatic roles, Zn also plays a critical role in controlling development. High Zn levels (ca. 1 mM) have been found in fish and frog eggs, and recently we have shown that the chemical environment of this Zn changes following fertilization. We are now using spectroscopy, microscopy, and biochemistry to characterize this Zn, and developing analytic methods for tracking the distribution of the Zn through cells during development. Why is Zn present in high concentrations, what roles does it play, and how it is able to control development?

We make extensive use of synchrotron radiation, using the unique resources available at synchrotron laboratories in the US (Brookhaven, Argonne, Stanford) and abroad (Japan, France). A key technique is X-ray absorption spectroscopy. This is one of the only ways to obtain detailed structural information for non-crystalline systems. In addition to X-ray methods, we make use of a wide range of other spectroscopies, including EPR, IR, and paramagnetically-shifted NMR.

AWARDS

• Camille and Henry Dreyfus Award for Newly Appointed Faculty in Chemistry
• Research Fellow of the Alfred P. Sloan Foundation
• Fogarty Senior International Fellowship, Centre d'Etude Atomique, Saclay, France
• Akron Section Award (American Chemical Society)
• 2003 Farrel Lytle Award

REPRESENTATIVE PUBLICATIONS

1. A.J. Wu, J.E. Penner-Hahn & V.L. Pecoraro, "Structural, Spectroscopic, and Reactivity Models for the Manganese Catalases", Chem. Rev. (2004) 104 , 903-938.
2. J.E. Penner-Hahn, "Characterization of 'Spectroscopically Quiet' Metals in Biology", Coord. Chem. Rev. (2005). 249 161-177.
3. T.-C. Weng, G.S. Waldo, J.E. Penner-Hahn, "A Method for Normalization of X-ray Absorption Spectra", J. Synchr. Rad. (2005), 12 , 506-510.
4. J. S. Magyar, T. C. Weng, C. M. Stern, D. Dye, B. W. Rous, J. C. Payne, B. M. Bridgewater, A. Mijovilovich, G. Parkin, J. M. Zaleski, J. E. Penner-Hahn, H. A. Godwin, "Reexamination of Lead(II) coordination preferences in sulfur-rich sites:   Implications for a critical mechanism of lead poisoning", (2005) J. Am. Chem. Soc ., 127 , 9495-9505.
5. D.E. Lansky, B. Mandimutsira, B. Ramdhanie, M. Clausén , J. Penner-Hahn, S. A. Zvyagin, J. Telser, J. Krzystek, R. Zhan, Z. Ou, K.M. Kadish, L. Zhakarov, A.L. Rheingold, & D.P. Goldberg, "Synthesis, Characterization, and Physicochemical Properties of Manganese(III) and Manganese(V)-Oxo Corrolazines" (2005) Inorg. Chem. , 44 , 4485-4498 .
6. M. Matzapetakis, D. Ghosh, T.-C. Weng, J.E. Penner-Hahn, & V.L. Pecoraro, "Peptidic Models for the Binding of Pb(II), Bi(III) and Cd(II) to Mononuclear Thiolate Binding Sites", (2006) J. Biol. Inorg. Chem. in press.