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There is now a CONTENT FREEZE for Mercury while we switch to a new platform. It began on Friday, March 10 at 6pm and will end on Wednesday, March 15 at noon. No new content can be created during this time, but all material in the system as of the beginning of the freeze will be migrated to the new platform, including users and groups. Functionally the new site is identical to the old one. webteam@gatech.edu
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Prof. Squire Booker, Pennsylvania State University
Taking a Hit for the Team: Self-Sacrifice as an Enzymatic Strategy in the Biosynthesis of Lipoic Acid
Lipoic acid is an eight-carbon straight-chain fatty acid containing sulfur atoms at carbons 6 and 8. In addition to its antioxidant properties, its most notable function is as a key cofactor that is employed by several multienzyme complexes that are involved in energy metabolism (pyruvate dehydrogenase and -ketoglutarate dehydrogenase complexes), or the catabolism of glycine (glycine cleavage system), branch-chain amino acids (branch-chain amino acid dehydrogenase complex), and acetoin (acetoin dehydogenase complex). In its role as a cofactor, it must be attached covalently in an amide linkage to the epsilon nitrogen of a specific lysine residue on a lipoyl carrying protein of the complex. This important post-translational modification can be achieved via two different mechanisms: one in which exogenous intact lipoic acid is activated and then appended to a lipoyl carrying protein, and one in which lipoic acid is constructed de novo in its cofactor form onto a lipoyl carrying protein.
This lecture will describe the characterization of lipoyl synthase, which catalyzes the terminal step in the de novo pathway for the biosynthesis of the lipoyl cofactor, which is the insertion of sulfur atoms at carbons 6 and 8 of an n-octanoyl chain that is covalently bound to lipoyl carrying proteins. Lipoyl synthase is a member of the radical-SAM superfamily of enzymes, wherein S-adenosylmethionine is used to generate a 5'-deoxyadenosyl 5'-radical, which is a required intermediate in catalysis. A working hypothesis for the role of the 5'-deoxyadenosyl 5'-radical will be presented, as will experiments that have been conducted to test that working hypothesis. Interestingly, data will be presented that indicate that the protein is both a catalyst and a substrate.
For more information contact Dr. Bridgette Barry (404-385-6085).
