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.
Huseby, M.J., A.C. Kruse, J. Digre, P.L. Kohler, J.A. Vocke, E.E. Mann, K.W. Bayles, G.A. Bohach, P.M. Schlievert, D.H. Ohlendorf, and C.A. Earhart. 2010. Beta toxin catalyzes formation of nucleoprotein matrix in staphylococcal biofilms. Proc. Natl. Acad. Sci. USA 107(32), 14407-12.
Hellberg, K., P.A. Grimsrud, A.C. Kruse, L.J. Banaszak, D.H. Ohlendorf, and D.A. Bernlohr. 2010. X-ray crystallographic analysis of adipocyte fatty acid binding protein (aP2) m odified with 4-hydroxy-2-nonenal. Prot. Sci. 19(8), 1480-9.
Hertzel, A.V., K. Hellberg, J.M. Reynolds, A.C. Kruse, B.E. Juhlmann, A.J. Smith, M.A. Sanders, D.H. Ohlendorf, J. Suttles, and D.A. Bernlohr. 2009. Identification and characterization of a small molecule inhibitor of fatty acid binding proteins. J. Med. Chem. 52(19), 6024-31.
Yoder, A.R., A.C. Kruse, C.A. Earhart, D.H. Ohlendorf, and L.R. Potter. 2008. Reduced ability of C-type natriuretic peptide (CNP) to activate natriuretic peptide receptor B (NPR-B) causes dwarfism in lbab(-/-) mice. Peptides 29(9), 1575-81.
McCormick, J.K., Bohach, G.A., Ohlendorf, D.H., & Schlievert, P.M. (2008). Exotoxins. In: The Staphylococci in Human Disease, 2nd Edition. Eds.: K.B. Crossley, and G.L. Archer. Churchill Livingstone, Inc.
Getun, I.V., Brown, C.K., Tulla-Puche, J., Ohlendorf, D., Woodward, C., & Barany, G. (2008). Partially folded bovine pancreatic trypsin inhibitor analogues attain fully native structures when co-crystallized with S195A rat trypsin. J. Mol. Biol. 375, 812-23.
Huseby, M., Shi, K., Brown, C.K., Digre, J., Mengistu, F., Seo, K.S., Bohach, G.A., Schlievert, P.M., Ohlendorf, D.H., & Earhart, C.A. (2007). Structure and biological activities of beta toxin from Staphylococcus aureu. J. Bacteriol. 189, 8719-8726.