CAA: Structural Studies on Multicopper Proteins

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The goal of this project is to determine the crystal structure of two multicopper proteins by X-ray diffraction techniques. The first protein, the multicopper oxidase phenoxazinone synthase (PHS) from Streptomyces antibioticus, catalyzes the penultimate step in the biosynthesis of actinomycin D. The second protein, a small metal binding protein (SmbP) from the ammonia oxidizing bacterium Nitrosomonas europaea, is capable of binding up to six Cu(II) ions and displays unusual thermal stability in the presence of this metal. The three dimensional structures of PHS and SmbP are not known and their structures will be determined to provide structural support for biochemical studies being conducted on these proteins. The long-term goal of this research is to understand the relationship between protein structure, function, stability and oligomeric assembly in metalloproteins. Multicopper oxidases have optimized intramolecular electron transfer rates suitable for the catalytic reduction of oxygen to water, an important reaction in biological systems and with significant implications for fuel cells and air batteries energy conversion. In addition, relatively little is known about the detailed mechanisms whereby multimeric proteins acquire their higher order structure, even though oligomeric proteins play important roles in a number of cellular processes. PHS could serve as a model system for the study of the role of protein structure, function and oligomer assembly. Structural studies on SmbP should provide important insights into the role of metal ions in protein stability and advance the field of protein folding and metalloprotein design.In terms of broader impacts, this research provides an excellent opportunity to train graduate and advanced undergraduate students in a multidisciplinary and multicultural research environment. The PI, a member of an underrepresented group, is actively involved in mentoring minority students at the undergraduate and graduate levels. The participation of undergraduate students in this project will be encouraged and emphasis will be placed on the recruitment of underrepresented minority students with the help of minority serving programs at Arizona State University.