The chief objective of this investigation is to clarify the mechanism of action of cardiac cytochrome oxidase. The interrelationships of cytochrome a and a3 and copper in the enzyme will be studied in heart muscle using spectrophotometric and electron paramagnetic (EPR) techniques as well as x-ray spectroscopy. An oxidase preparation depleted of EPR-visible copper or of total copper will be used in these studies. Efforts will also be made to reconstitute copper into the depleted enzyme. A cytochrome oxidase from Pseudomonas aeruginosa will be studied as a model for the cardiac enzyme. Research will include crystal structure, liganding of heme groups, sites of heme binding relative to the three-dimensional structure of the protein, and kinetics of oxygen and nitrite reduction. The purpose of these investigations is to help understand the bioenergetic processes of heart muscle in health and disease.
| Steup, M B; Muhoberac, B B (1989) Preparation and spectral characterization of the heme d1.apomyoglobin complex: an unusual protein environment for the substrate-binding heme of Pseudomonas cytochrome oxidase. J Inorg Biochem 37:233-57 |
| Horowitz, P; Muhoberac, B B; Falksen, K et al. (1986) Perturbation of Pseudomonas cytochrome oxidase by guanidine hydrochloride to detect differential stabilization of the heme d1 and heme c moieties. Biochim Biophys Acta 871:142-8 |
