BIOL 213 |
| Cardiovascular disease and cancer are leading causes of death for the people in western countries. The inactivation of enzymes involved in mevalonate pathway is one major method for treating diseases. The first step of mevalonate pathway is catalyzed by cytosolic thiolase. In our study , we found that the enzyme has intrinsic isomerase activity. The isomerase activity of the enzyme was thoroughly characterized. We also found that C382 is the catalytic residue for both thiolase and isomerase activities of the enzyme. Based on this result, we further synthesized 2-octynoyl-CoA as an isomerase mechanism-based inhibitor. Through trypsin digestion, separation of HPLC and analysis of MS/MS data, we found C92 was covalently labeled by the inhibitor. Inactivation of thiolase by 2-alkynoyl-CoA via its intrinsic isomerase activity may provide an alternative better solution for treatment of cardiovascular disease and cancer, and a novel example for the design of mechanism-based inhibitors. |
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Frontiers in Chemical Biology
5:00 PM-7:00 PM, Wednesday, August 22, 2007 BCEC -- Exhibit Hall - B2, Poster
Division of Biological Chemistry |