The work proposed in this competing renewal application is to continue studies on transition metalloproteins, whose metal centers can be examined by various physical probes. As a first aim, we should like to develop quantitative aspects of electron spin echo spectroscopy. In particular, we should like to study electron-deuteron interactions in low spin heme and Cu(II) compounds where deuterium is specifically bound on a metal ligand. We will use this information for the determination of radial distances to specifically deuterated substrates bound to enzymes. In another study, we should like to vary electron supplying and withdrawing substituents on imidazole, determine the contact interactions with the remote nitrogen, and relate this to the binding constant for the ligand to Cu(II). As a second aim, we would like to study the mechanism of bleomycin degradation of DNA, with particular attention to oxygen activation and to oxidative lesions in DNA. Such questions as metal exchange, redox cycling and metal substitution as might be relevant to an in vivo situation will be addressed. It is anticipated that the descriptive chemistry that will be learned from this problem will be applicable to our understanding of the mechanisms of various oxygenases, especially cytochrome P-450.
A third aim, is to convert stellacyanin to a form that can be crystallized so that the metal-ligand structure can be determined by X-ray analysis. Finally, we should like to study the physical properties of hydroxyindole oxidase as a specific model for cytochromes a3. Information forthcoming from these studies would also be relevant to bimetallic centers, such as the type 3 copper site of laccase.
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