Contact InformationOffice: MBB: 2.106
Lester J. Reedlreed@utexas.edu
Ashbel Smith Professor Emeritus
Merck Award, American Society for Biochemistry and Molecular Biology, 1994
Fellow, American Academy of Arts and Sciences, 1981
Member, National Academy of Sciences, USA, 1973
Eli Lilly & Co. Award in Biological Chemistry, ACS, 1958
Enzyme structure, function, and regulation
Research is directed toward elucidating the structure, function, and regulation of the alpha-keto acid dehydrogenase multienzyme complexes from eukaryotic and prokaryotic cells. My group has isolated pyruvate, alpha-ketoglutarate and branched chain alpha-keto acid dehydrogenase in a highly purified state. These enzyme complexes, which have molecular weights ranging from 2.5 to 9.5 million, have been separated into their component enzymes. The individual enzymes have been characterized, and the complexes have been reconstituted from the isolated enzymes. Structural studies, including electron microscopy, X-ray diffraction, and protein engineering are directed toward elucidating the manner in which the individual enzymes are held together and interact in these complexes. We have shown that the activity of the mammalian pyruvate dehydrogenase complex is regulated by a phosphorylation-dephosphorylation cycle, catalyzed by a specific protein kinase and a protein phosphatase. The kinase and the phosphatase have been isolated in a near homogeneous state from bovine kidney mitochondria. cDNAs, encoding the two subunits, catalytic and regulatory, comprising the phosphatase have been cloned, sequenced, and expressed. Structure-function relationships in the phosphatase are being investigated by protein engineering. Determination of the crystal structure of the catalytic subunit is in progress.
"On the Unique Structural Organization of the Saccharomyces cerevisiae Pyruvate Dehydrogenase Complex" J. Biol. Chem. 272 (1997): 5757-64.
"Role of the regulatory subunit of bovine pyruvate dehydrogenase phosphatase" Proc. Natl. Acad. Sci., USA 93 (1996): 4953-6.
"Molecular Cloning and Expression of the Catalytic Subunit of Bovine Pyruvate Dehydrogenase Phosphatase and Sequence Similarity with Protein Phosphatase 2C" Biochemistry 32 (1993): 8987-93.
"Structure-Function Relationships in Dihydrolipoamide Acetyltransferases" J.Biol.Chem. 265 (1990): 8971-4.