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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, chromatin and epigenetics. 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: Brent, M.M., Iwata, A., Carten, J., Zhao, K. and Marmorstein, R. (2009) “Structure and biochemical characterization of protein acetyltransferase (PAT) from Sulfolobus Solfataricus” J. Biol. Chem. In press Xie, P., Streu, G., Qin, J., Bregman, H., Pagano, N., Meggers, E., Marmorstein, R. (2009) “Crystal structure of BRAF in complex with an organoruthenium inhibitor reveals a mechanism for inhibition of an active form of BRAF kinase” Biochemistry 48:5187-5198. Malecka, K.A., Ho, W.C. and Marmorstein, R. (2009) “Crystal structure of a p53 core domain tetramer bound to DNA” Oncogene 28:325-333. Tang, Y., Meeth, K., Jiang, E., Luo, C. and Marmorstein, R. (2008) “Structure of Vps75 and implications for histone chaperone function” Proc. Natl. Acad. Sci. 105:12206-12211. Tang, Y., Holbert, M.A., Wurtele, H., Meeth, K., Rocha, W., Gharib, M., Jiang, E., Thibault, P., Verreault, A., Cole, P.A. and Marmorstein, R. (2008) “Fungal Rtt109 histone acetyltransferase is an unexpected structural homolog of metazoan p300/CBP” Nature Struc. Mol. Biol. 15:738-745. 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. 3:305-316. 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. |
