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327 Wistar Institute |
The laboratory uses a broad range of molecular, biochemical and biophysical research tools centered on X-ray crystal structure determination to understand the mechanism of macromolecular recognition and post-translational histone and protein modifications in the regulation of gene expression. The laboratory is particularly interested in gene regulatory proteins and kinases that are aberrantly regulated in cancer and age-related metabolic disorders such as type II diabetes and obesity, and the use of high-throughput small molecule screening and structure-based design strategies towards the develop protein-specific small-molecule compounds to treat such diseases. Selected Publications: Xie, P., Williams, D.S., Atilla-Gokcumen, G. E., Milk, L., Xiao, M., Smalley, K.S.M., Herlyn, M., Meggers, E., and Marmorstein, R. (2008) Structure-based design of an organoruthenium Phosphatidyl-Inositol-3-Kinase inhibitor reveals a switch governing lipid kinase potency and selectivity. ACS Chem. Biol. (In press) Liu, X., Wang, L., Zhao, K., Thompson, P.R. Hwang, Y., Marmorstein, R. and Cole, P.A. (2008) The structural basis of protein acetylation by the p300/CBP transcriptional coactivator. Nature 451:846-850. Liu, X. and Marmorstein, R. (2007) Structure of the retinoblastoma protein bound to adenovirus E1A reveals the molecular basis for viral oncoprotein inactivation of a tumor suppressor. Genes Dev., 21:2711-2716. Holbert, M.A., Sikorski, T., Carten, J., Snowflack, D., Hodawadekar, S and Marmorstein, R. (2007) The human monocytic leukemia zinc-finger histone acetyltransferase domain contains DNA binding activity implicated in chromatin targeting. J. Biol. Chem. 282:36603-36613. Sanders, S.D., Zhao, K., Slama, J.T. and Marmorstein, R. (2007) Structural basis for nicotinamide inhibition and base exchange in Sir2 enzymes. Mol. Cell, 25:463-472. |
