Portfolio Press Release
UT Southwestern Medical Center Uses the Fluidigm TOPAZ System to Determine the Structure of the PCSK9/EGF-A Complex
The Findings Could Lead to the Development of New Therapeutics for Lowering Harmful Cholesterol
Fluidigm Press Release
26 March 2008
SOUTH SAN FRANCISCO, Calif. — (BUSINESS WIRE) — Fluidigm has announced that the TOPAZ® system has been used to determine the structure of PCSK9 complexed with the EGF-A domain of the LDL receptor. PCSK9 is a protein that binds to LDL receptors and prevents them from removing LDL cholesterol in the blood. High levels of LDL cholesterol can cause the buildup of harmful plaques in arteries and increase the risk of heart disease and stroke. The findings could lead to the development of new therapeutics for lowering harmful cholesterol. The full details of the structure are described in an article titled "Molecular basis for LDL receptor recognition by PCSK9", published in the February 12, 2008 issue of PNAS.
"The TOPAZ system allowed us to screen many more crystallization conditions than would otherwise have been possible considering the limited availability of the sample," says Dr. Hyock Kwon, Instructor from the Johann Deisenhofer Lab at the University of Texas Southwestern Medical Center. "The total amount of protein that was used to complete the entire project was still less than what we would have used just to screen 20 percent of these conditions by conventional methods."
Researchers used the TOPAZ screening chips to identify initial crystallization conditions of the PCSK9/EGF-A complex. The crystals were then reproduced using microbatch methods under Al's oil to produce diffraction-quality crystals. X-ray data was collected at the Advanced Photon Source and the structure was solved to 2.4 Ångströms.
TOPAZ screening chips are capable of running up to 768 experiments in parallel using only 1 microliter of protein per 96 conditions. The TOPAZ system also includes the most effective analysis software for scoring crystals and managing the vast amount of data obtained from crystallization experiments. The system is unique because it uses integrated fluidic circuits (IFCs)-a network of channels, valves and chambers-designed for crystallization using the free interface diffusion technique.
About Fluidigm Corporation
Fluidigm Corporation develops and distributes systems based on the unique properties of integrated fluidic circuits (IFCs) to control precisely fluids on a nanoliter volume scale. The Company's vision is to create and to lead a new industry in which IFCs bring unparalleled efficiencies to the life science and allied fields. Based in South San Francisco, California, the Company is privately held and backed by premier investors: Versant Ventures, Euclid SR Partners, InterWest Partners, Alloy Ventures, Lehman Brothers Healthcare Fund, Bio*One Capital, Bruce Burrows, Lilly BioVentures, the Invus Group, SightLine Partners, AllianceBernstein, Wasatch Advisors and its affiliate, Cross Creek Capital, and GE Equity.
