This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Acyl-CoA dehydrogenases are a family of enzymes that are involved in the first oxidative step in the mitochondrial catabolism of fatty acids and in the catabolism of some amino acids. ETF funnels the reducing equivalents to the main mitochondrial respiratory chain via ETF-ubiquinone oxidoreductase (ETF-QO), a membrane-bound, iron-sulfur flavoprotein; it is also proposed to determine the structure of ETF-QO. Fatty acid oxidation is the principal energy-yielding process in the liver, kidney, and skeletal muscle. The rate of this process can be altered by diet, physiological status, and disease, exemplified by starvation, pregnancy, and diabetes. The critical roles played in metabolism by acyl-CoA dehydrogenases, ETF, and ETF-QO, is illustrated by the severity of human diseases resulting from inherited deficiencies of each of these enzymes. We plan to determine the structures of two acyl-CoA dehydrogenases that have not been determined yet. Long chain acyl-CoA dehydrogenase and glutaryl-CoA dehydrogenase, both of which we have obtained high resolution crystals. Mitochondrail enoyl-CoA isomerase is a relatively small dimeric enzyme (32 kDa/subunit). It's function complements eukaryotic DCR in the metabolizm of unsaturated fatty acids. Data was collected to 2.5 A on our last visit to BioCARS, and most of the structure has been solved. However, there unusual C-terminal alpha-helical domain requires futher data for side-chain assignment, and an EXAFS scan is needed to assess if a metal ion is bound to the enzyme (possibly zinc. In addition, recently we have obtained better crystals that diffract to 1.8A at home. We would like to collect a very high resolution data set.
Showing the most recent 10 out of 120 publications