Timothy L. Stemmler, Ph.D.

Our lab uses a variety of spectroscopic techniques to characterize the structure and function of a series of proteins involved in regulating cellular metal homeostasis and oxidative stress, as well as enzymes that confer antibiotic resistance in bacteria. Our lab is interested in understanding the role of the mitochondrial protein "Frataxin" in regulating mitochondrial iron biochemistry, heme biosynthesis and iron-sulfur cluster assembly. The second major project in my lab is characterizing how the structural and dynamic properties of b-lactamase proteins help confer antibiotic resistance in bacteria; b-lactamases chemically modify b-lactam antibiotics (penicillins, etc.) making bacteria resistant to this class of drugs. One of the spectroscopic tools our lab uses to characterize these proteins is nuclear magnetic resonance (NMR) spectroscopy. NMR spectroscopy is widely accepted as the premiere technique for characterizing the dynamic behavior of biomolecules, in addition to providing structural detail at the atomic level, in solution. X-ray absorption spectroscopy (XAS) is the second solution-based technique our lab uses to characterize the structural properties of metal centers in metal binding proteins. Finally, we use a variety of spectrophotometric techniques (UV-Vis, CD, stop-flow, etc.) to characterize the biochemistry performed by our proteins.

Proteasa, S.; He, Y.; Stemmler, T.L. Understanding the nature of iron binding to monomeric yeast frataxin. Manuscript in Preparation.

He, Y.; Zhang, Y.; Alam, S.L.; Sundquist, W.I.; Stemmler, T.L. The solution structure and dynamics of the apo-yeast frataxin homoloque protein Yfh1p: Insights into iron binding. Manuscript in Preparation.

Golemi, D.; Meroueh, O; Kim, C; Vakulenko, V; Bulychev, A; Stemmler, A.J.; Stemmler, T.L.; Mobashery, S. The Importance of a Critical Protonation State and the Fate of the Catalytic Steps in Class A b-Lactamases. J. Biol. Chem., Submitted.

Wang, B.; Alam, S.L.; Meyer, H.H.; Payne, M.; Stemmler, T.L.; Davis, D.R.; Sundquist, W.I. Structure and Ubiquitin Interactions of the Conserved NZF Domain of Npl4. J. Biol. Chem., 2003, 278:20225- 20234, 2003

Lieberman, R.L.; Shrestha, D.; Doan, P.E.; Hoffman, B.M.; Stemmler, T.L.; Rosenzweig, A.C. Purified particulate methane monooxygenase from Methylococcus capsulatus (Bath) is a dimer with both mononuclear copper and a copper-containing cluster. Proc. Natl. Acad. Sci. 100:3820-3825, 2003.

Schwedler, U.v.; Stemmler, T.L.; Klishko, V.Y.; Albertine, K.H.; Davis, D.R. .; Sundquist, W.I. Proteolytic Refolding of the Amino-terminus of the HIV-1 Capsid Protein Helps Trigger Viral Maturation. EMBO J. 17:1555-1568, 1998.

Stemmler, T.L.; Sossong, T.R.; Ash, D.E.; Elgren, T.; Kurtz, D.; Penner-Hahn, J.E. EXAFS Comparison of the Dimanganese Core Structure of Manganese Catalase, Arginase and Manganese-Substituted Ribonucleotide Reductase and Hemerythrin. Biochemistry, 36:9847-9858, 1997.