Roger Fenna 

Professor of Biochemistry and Molecular Biology

Ph.D. (1973) Oxford University, UK

X-ray Crystallography, Protein Structure and Function

Tel: (305) 243-6564, Fax: (305) 243-3065

rfenna@med.miami.edu

 

My laboratory is involved in determination of the three-dimensional structures of protein molecules by X-ray crystallography. Knowledge of the tertiary structures of enzymes and other proteins can be applied to understanding the mechanisms by which these macromolecules carry out their biological functions. X-ray crystallography is a powerful technique that can be used in conjunction with site-directed mutagenesis to not only understand the catalytic mechanisms of existing enzymes; but also to engineer new macromolecules of potentially significant use in both medicine and a variety of industrial applications.

Recently, we have determined the structure of human myeloperoxidase, an enzyme that catalyses the peroxidation of chloride ions to hypochlorite in white blood cells. This reaction is important in the anti-viral and anti-bacterial activities of these cells. We have found that the unusual green color of this enzyme results from chemical bonds between the heme and the protein and we are continuing to explore the mechanism of catalysis of this powerful oxidising enzyme.

Human Myeloperoxidase

Myeloperoxidase is the only known mammalian enzyme that can catalyse the biosynthesis of 'bleach' from hydrogen peroxide and sodium chloride. Previously my laboratory has worked on structural studies of chlorophyll containing proteins that play important roles in photosynthesis and milk proteins involved in the biosynthesis of the milk sugar lactose. In the future we hope to investigate the structures of human transcription factors that bind to DNA and other proteins that participate in the in vivo folding of protein molecules such as the enzyme protein disulfide isomerase.

Representative Publications

1. Blair-Johnson, M., Fiedler, T.J., and Fenna, R.E.  “Human Myeloperoxidase: Structure of a Cyanide Complex and its Interaction with Bromide and Thiocyanate Substrates at 1.9 A Resolution.” Biochemistry, 40, 13990-13997 (2001).
2. Fiedler, T.J., Davey, C.A., and Fenna, R.E. “X-ray Crystal Structure and Characterization of Halide-binding Sites of Human Myeloperoxidase at 1.8 A Resolution.” J. Biol. Chem., 275, 11964-11971 (2000).
3. Corollo, D., Blair-Johnson, M., Conrad, J., Fiedler, T., Sun, D., Wang, L., Ofengand, J., and Fenna, R.E. “Crystallization and Characterization of a Fragment of Pseudouridine Synthase RluC from E. coli.” Acta Cryst. D55, 302-304 (1999).
4. Davey, C.A., and Fenna, R.E. “2.3 Å Resolution X-ray Crystal Structure of the Bi-substrate Analogue Inhibitor Salicylhydroxamic Acid Bound to Human Myeloperoxidase: A Model for a Pre-reaction Complex with Hydrogen Peroxide.” Biochemistry 35, 10967-10973 (1996).
5. Fenna, R.E., Zeng, J., and Davey, C. “Structure of the Green Heme in Myeloperoxidase.” Archiv. Biochem. And Biophys., 316, 653-656 (1995).

Honors and Professional Activities

·         American Crystallographic Association.

·         N.I.H. Research Career Development Awardee (1983-1988)