Lei Li
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Assistant Professor
Bioinorganic chemistry, Bioorganic chemistry, Enzymology.
DNA photo damage and repair, RNA modification |
| Ph.D. The Johns Hopkins University 1999-2005
Postdoctoral fellow University of Michigan 2005-2009
Member, The American Chemical Society
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| Phone: (317) 278-2202 |
| Email: lilei@iupui.edu |
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Research
Mechanistic studies of DNA repair enzyme spore photoproduct lyase (SPL)
(Funded by NIEHS through a R00 grant)
Endospore-forming bacteria are responsible for a number of serious diseases in humans, including anthrax and botulism. Infectious endospores are extremely resistant to a number of harsh environments. Their unusual tolerance to high-dose UV irradiation arises from the action of spore photoproduct lyase (SPL) - a metalloenzyme that repairs the "spore photoproduct" dithymine DNA lesion. SPL uses a 5'-deoxyadenosyl (5'-dA) radical, formed from reductive cleavage of S-adenosylmethionine (SAM), to initiate lesion repair, but little else is known about its mechanism. The objectives of the project are: (1) To understand the photochemistry of thymine damage. We will employ thymine and its analogs to explore the influence on the reaction rates/yields. (2) To identify critical SPL-substrate interactions. We will evaluate SP repair in different DNA local environments. (3) To reveal the detailed reaction mechanism. We will measure the deuterium isotope effect to shed light on the reaction energy surface, examine reaction reversibility, and probe the radical intermediates with various mechanism-based inhibitors. (4) To understand the radical initiation reaction in SPL. We will determine the redox potential of the unique [Fe4S4] cluster, coupled with key amino acids mutagenesis studies.
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Recent Publications
Li, L.; Paterson, D. P.; Lin, B.; Coschigano, P. W.; Marsh, E. N. G. "The Subunit Structure of Benzylsuccinate Synthase" Biochemistry, 2008, Submitted.
Li, L.; Marsh, E. N. G. "Mechanism of Benzylsuccinate Synthase Probed by Substrate and Isotope Exchange" Journal of the American Chemical Society, 2006, 128, 16056-16057.
Li, L.; Marsh, E. N. G. "Deuterium Isotope Effects in the Unusual Addition of Toluene to Fumarate Catalyzed by Benzylsuccinate Synthase" Biochemistry, 2006, 45, 13932-13938.
Li, L.*; Lucas, H. R.*; Sarjeant,; A. A.; Vance, M. A.; Solomon, E. I.; Karlin, K. D. "Aliphatic C-H Bond Oxidations Initiated by a µ-1,2-Peroxodicopper(II) Complex" Journal of the American Chemical Society, 2008, Submitted (* equal contribution).
Li, L.; Telser, J.; Murthy, N. N.; Zakharov, L. V.; Yap, G; Rheingold, A. L.; Karlin, K.D.; Rokita, S. E. "Targeted guanine oxidation by a dinuclear copper(II) complex at single stranded/double stranded DNA junctions" Inorganic Chemistry, 2006, 45, 7144-7159.
Li, L.; Sarjeant, A. A.; Karlin, K. D. "Reactivity study of a hydroperoxodicopper(II) complex: hydroxylation, dehydrogenation, and ligand cross-link reactions" Inorganic Chemistry, 2006, 45, 7160-7172.
Li, L.; Sarjeant, A. A.; Vance, M. A.; Zakharov, L. V.; Rheingold, A. L.; Solomon, E. I.; Karlin, K. D. "Exogenous Nitrile Substrate Hydroxylation by a New Dicopper-hydroperoxide Complex" Journal of the American Chemical Society, 2005, 127,15360-15361.
{Highlighted in the Science magazine section on "Highlights of Recent Literature, Editor's Choice", Science, 2005, 310, 591}
Li, L.; Karlin, K. D; Rokita, S. E. "Changing Selectivity of DNA Oxidation from Deoxyribose to Guanine by Ligand Design and a New Binuclear Copper Complex" Journal of the American Chemical Society, 2005, 127, 520-521.
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