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G.R. Hoffman, N. Nassar, and R.A. Cerione
Departments of Molecular Medicine, and Chemistry and Chemical Biology, Vet Medical Center, Cornell University, Ithaca, New York

[Cell, Vol 100, 345-356 (2000).]

Cancer researchers have made a structural map of cellular switches called Cdc42 complexed with GDI(guanine nucleotide-dissociation inhibitor). The structural mapping was obtained with x-ray crystallographic methods from data collected with MacCHESS resources at CHESS. MacCHESS, a NIH supported resource, builds and operates the specialized x-ray detectors and cameras needed to collect the data from crystals grown of this complex.

The results of the diffraction analysis are given in the figure at the right. Here groups of atoms are shown as ribbons of connected structure. The regulatory arm (blue) of the structure binds to switch I (pink) and switch II (orange) regions, giving the researcher a three-dimensional physical picture of the inhibited state.

Additional biochemistry studies [1] show how a hyperactive form of the Cdc42 molecular switch can increase the shuttling of other proteins throughout the cell thus disrupting the orderly cell growth. If the Cdc42 part is mutated and switched on for an extended period of time, the cellar activities are overstimulated, thus producing malignant cells, i.e. cancer.

This discovery offers potential targets for drugs to block tumor growth.

This research was made possible by the operation of CESR (Cornell Electron – Positron Storage Ring) a NSF supported high-energy storage ring designed for particle physics and CHESS, a NSF laboratory supporting both material science and biological work. This work illustrates how important integrated facilities with various interdisciplinary staff are contributing to ongoing fundamental cancer research.

1. W.J. Wu, J. W. Erickson, R. Lin, & R. A. Cerione, Nature, Vol 405, 15 June 2000, 800-801.