Research Interests   Protein Engineering; Structural and Molecular Biology; X-ray Crystallography

My lab is interested in the structural foundations for biological function. Just as a picture is worth a thousand words, we believe a structure is worth a thousand pictures. Hypotheses suggested by the structures are tested through mutagenesis followed by biophysical characterization of mutants.

We study a diverse range of proteins. One group are metalloenzymes involved in degrading organic compounds in the environment. Here we look at metal ion and substrate selectivity, structural changes during the catalytic process,  targeting substrate sites for chemical attack. A second group of proteins are virulence factors in gram positive pathogens. These molecules function through interactions with other macromolecules. Through these studies novel diagnostic and therapeutic strategies can be developed.

Earhart, C. A., Vath, G. M., Roggiani, M., Schlievert, P. M. & Ohlendorf, D. H. (2000). Structure of streptococcal pyrogenic exotoxin A reveals a novel metal cluster. Protein Sci.   9 (9), 1847-51.

Mitchell, D. T., Levitt, D. G., Schlievert, P. M. & Ohlendorf, D. H. (2000). Structural evidence for the evolution of pyrogenic toxin superantigens.   J. Mol. Evol. 51 (6), 520-31.

Rago, J.V., Vath, G.M., Bohach, G.A., Ohlendorf, D.H., Schlievert, P.M. (2000) "Mutational analysis of the superantigen staphylococcal exfoliative toxin A (ETA)." J. Immunol. 164(4):2207-13.

Roggiani, M., Stoehr, J. A., Olmsted, S. B., Matsuka, Y. V., Pillai, S., Ohlendorf, D. H. & Schlievert, P. M. (2000). Toxoids of streptococcal pyrogenic exotoxin A are protective in rabbit models of streptococcal toxic shock syndrome. Infect. Immun. 68 5011-7.

Brown, C. K., Vetting, M. W., Earhart, C. A. & Ohlendorf, D. H. (2004). Biophysical analyses of designed and selected mutants of protocatechuate 3,4-dioxygenase. Annu. Rev. Microbiol. 58 555-85.

Vetting, M.W., Ohlendorf, D.H. (2000) "The 1.8 A crystal structure of catechol 1,2-dioxygenase reveals a novel hydrophobic helical zipper as a subunit linker." Structure Fold Des. 8(4):429-40.

Brown, C. K., Gu, Z.-Y., Matsuka, Y. V., Purushothaman, S. S., Winter, L. A., Cleary, P. P., Olmsted, S. B., Ohlendorf, D. H. & Earhart, C. A. (2005). Structure of the streptococcal cell wall C5a peptidase. Proc. Natl. Acad. Sci. U. S. A. 102 (51), 18391-18396.

Earhart, C. A., Vetting, M. W., Gosu, R., Michaud-Soret, I., Que, L. J. & Ohlendorf, D. H. (2005). Structure of catechol 1,2-dioxygenase from Pseudomonas arvilla. Biochem. Biophys. Res. Commun. 338 (1), 198-205.

Shi, K., Brown, C. K., Gu, Z.-Y., Kozlowicz, B. K., Dunny, G. M., Ohlendorf, D. H. & Earhart, C. A. (2005). Structure of peptide sex pheromone receptor PrgX and PrgX/pheromone complexes and regulation of conjugation in Enterococcus faecalis. Proc. Natl. Acad. Sci. U. S. A. 102 (51), 18596-18601.