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Ph.D., 1976, Southampton University (Biochemistry) 130C John Morgan
Building |
The aldo-keto reductase (AKR) superfamily: roles in steroid hormone action and mechanisms of carcinogen activation. Structure-function studies are being performed on discrete AKR isoforms that regulate the occupancy and trans-activation of steroid hormone receptors. The goal is rational drug-design. Some AKRs are implicated in the metabolic activation of polycyclic aromatic hydrocarbons which are human carcinogens by forming reactive and redox-active o-quinones. The DNA-damaging events that result from quinone formation and the mutational consequences of these lesions are being studied.
Selected Publications: Shultz, C., Palackal, N., Mangal, D., Harvey, R., Blair, I.A., and Penning, T.M. (2008) Fjord-region benzo[g]chrsyene-11,12-dihydrodiol and benzo[c]phenantherne-3,4-dihydrodiol as substrates for rat liver dihydrodiol dehydrogenase (AKR1C9): Structural basis for stereochemical preferences. Chem Res Toxicol. 21:668-667. [Profiled as an Editorial] Cooper, W.C., Jin, Y., and Penning, T.M. (2007) Elucidation of a complete kinetic mechanisms for a mammalian hydroxysteroid dehdyrogenase (HSD) and identification of all enzyme forms on the reaction coordinate: The example of rat liver 3α-HSD (AKR1C9). J. Biol. Chem. 282:33484-33493. Jiang, H., Gelhaus, S.L., Mangal, D., Harvey, R.G., Blair, I.A. and Penning, T.M. (2007) Metabolism of benzo[a]pyrene in human bronchoalveolar H358 cells using liquid chromatography-mass spectrometry. Chem. Res. Toxicol. 20:1331-41. (Listed as a most cited article in ACS journals in 2007). Penning, T.M., Steckelbroeck, S., Bauman, D.R., Miller, W.M., Jin, Y., Peehl, D.M., Fung, K-M. and Lin, H.K. (2006) Aldo-keto reductase (AKR) 1C3: Role in prostate disease and the development of specific inhibitiors. Mol. Cell. Endocrinol. 248:182-191. Yee DJ, Balsanek V, Bauman DR, Penning T.M., Sames D. (2006) Fluorogenic metabolic probes for direct activity readout of redox enzymes: Selective measurement of human AKR1C2 in living cells. Proc Natl Acad Sci U S A. 103:13304-13309. Penning, T.M., Burczynski, M.E., Hung, C-F., McCoull, K., Palackal, N. and Tsuruda, L.S. (1999) Dihydrodiol dehydrogenases and polycyclic aromatic hydrocarbon activation: Generation of reactive and redox active o-quinones. Chem. Res. Toxicol. 12:1-18. (Cover Feature and a Most Cited Article in ACS journals in 10 years) |
